bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5973Regional left ventricular myocardial work and response to cardiac resynchronization therapy
Authors: Kostyukevich M V , Van Der Bijl P , Vo N M , Ajmone Marsan N , Delgado V , Bax J J 
Published: October 2019

Abstract

Background
Myocardial work, assessed by speckle tracking echocardiography, reflects mechanical efficiency of the left ventricle. In heart failure patients, characterization of acute changes in regional (septal and lateral) left ventricular (LV) myocardial walls after cardiac resynchronization therapy (CRT) may enhance understanding of CRT response.

Objective
To evaluate the interaction between CRT response and components of myocardial work of the lateral wall and septum in patients with heart failure.

Methods
Regional LV myocardial work was calculated by integrating non-invasive blood pressure measurements, timing of mitral and aortic valve opening and closure and speckle tracking-derived LV longitudinal strain. From pressure-strain loops, constructive work (CW) and wasted work (WW) were calculated. CRT response was defined as a decrease in LV end-systolic volume ≥15% at 6 months follow-up. Changes in CW and WW of the septal and lateral walls prior to (baseline) and within the first 5 days after CRT implantation were compared between CRT responders and non-responders.

Results
At baseline, measurement of regional CW and WW was performed in 168 patients treated with CRT (71% men, 66±10 years). At 6 months, 59% of patients were CRT responders. CRT responders more frequently had non-ischemic heart failure than non-responders (54% vs 36%; p=0.027). At baseline, CRT responders were characterized by a significantly higher septal WW (270.5 [160.0; 451.5] mmHg% vs. 210.5 [106.3; 336.5] mmHg%; p=0.038) and lateral CW (989.5 [574.0; 1439.0] mmHg% vs. 689.0 [463,3; 1140.0] mmHg%; p=0.005). On multivariable analysis, only CW of the lateral wall at baseline was independently associated with CRT response (HR 1.001; 95% CI, 1.000–1.001; p=0.048).
Immediately after CRT implantation, measurement of regional CW and WW was feasible in 115 patients. CRT responders showed improvement in CW (433.0 [254.5; 686.5] mmHg% to 664.5 [424.5; 977.8] mmHg%; p<0.001) and WW (305.0 [169.0; 461.3] mmHg% to 145.0 [80.0; 306.3] mmHg%; p=0.005) of the septum whereas the lateral wall demonstrated a significant decrease in CW (1036.5 [561.0; 1402.0] to 818.0 [491.0; 1154.3] mmHg%; p=0.005) and increase in WW (132.5 [80.3; 269.3] to 198.5 [107.5; 331.0] mmHg%; p=0.025). Non-responders showed only a decrease in WW of the septum (202.8 [102.9; 332.5] to 168.5 [67.6; 258.4] mmHg%; p=0.049).

Conclusion
CRT responders are characterized by increased WW of the septum and CW of the lateral wall at baseline, which are corrected immediately after CRT implantation. Constructive work of the LV lateral wall at baseline is independently associated with CRT response.

Acknowledgement/Funding
Study was supported by ESC Research grant 2018
P5976Prediction of ventricular arrhythmias with mechanical dispersion assessed by strain echocardiography: a systematic review and meta-analysis
Authors: Kawakami H , Nerlekar N , Haugaa K H , Edvardsen T , Marwick T H 
Published: October 2019

Abstract

Background
Recent studies have demonstrated that left ventricular mechanical dispersion (LVMD) assessed by speckle tracking might be a powerful marker in risk stratification for ventricular arrhythmias (VA). We sought to perform a systematic review and meta-analysis to i) assess the prognostic value of this parameter (previous studies were predominantly single-center), ii) define the value relative to other parameters, iii) identify the most appropriate cutoff for designating risk.

Purpose
To assess the association between LVMD and the incidence of VA.

Methods
A systemic review of studies reporting the predictive value of LVMD for VA was undertaken from a search of Medline and Embase. LVMD was defined as the standard deviation of time from Q/R on ECG to peak negative strain from each LV segment. VA events were defined as sudden cardiac death, cardiac arrest, documented ventricular tachyarrhythmia, and appropriate implantable cardioverter defibrillator therapy. Hazard ratios (HRs) were extracted from univariable and multivariable models reporting on the association of LVMD and VA and described as pooled estimates with 95% confidence intervals (CIs). In a meta-analysis, the predictive value of LVMD was compared to that of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS).

Results
Among 3198 patients (weighted mean, 63 years, 30% female; 82% ischemic heart disease) in 12 published articles, 387 (12%) had VA events over a follow-up (17–70 months). Patients with VA events had a significantly greater mechanical dispersion compared with those without VA events (weighted mean difference, −20.3 ms; 95% CI, −27.3 to −13.2; p<0.01); 60 ms was found to be the optimal cutoff LVMD value for predicting VA events. Each 10 ms increment of LVMD was significantly and independently associated with VA events (HR, 1.19; 95% CI, 1.09 to 1.29; p<0.01). The predictive value of LVMD was superior to that of LVEF or GLS (Figure).
Figure 1

Conclusion
LVMD assessed by speckle tracking provides important predictive value for VA in patients with a number of cardiac diseases and appears to have superior predictive value to LVEF and GLS for risk stratification.
P5985New aspects of management of patients with long-term persistent atrial fibrillation before extracardiac interventions
Authors: Dzhioeva O , Resnik E , Nikitin I 
Published: October 2019

Abstract
Surgery in patients with atrial fibrillation is always an additional risk of thromboembolic complications. In the modern era of direct oral anticoagulants, the risk of bleeding is much lower, due to the lack of need for a Bridge, but at the same time, there is no clear position on the strategy of management of patients with long-term current atrial fibrillation in the tactics of rhythm control or heart rate control.
In our clinic we examined 772 before surgical intervention high risk. Of these, atrial fibrillation was diagnosed in 366 patients. 121 patients had a persistent or long-persistant form of arrhythmia. To determine the tactics, we performed a transesophageal echocardiographic study to assess intracardiac hemorheology. 109 studies were performed. 35 patients received rivaroxaban, 29 dabigatran, 19 apixaban, 26 patients did not receive anticoagulant therapy. Disorders of intracardiac hemorheology that do not allow to perform a planned cardioversion, such as blood clots and spontaneous contrast 3–4 degrees, were detected in 78% of patients not receiving anticoagulant therapy, 56% of patients receiving dabigatran, 52% of patients receiving rivaroxaban and 38% of patients receiving apixaban. Among patients with disorders of intracardiac hemorheology, unreasonably reduced doses were taken by 78% of patients. Patients with thrombotic disorders proposed to enter the perioperative period in accordance with the strategy of heart rate control and correction doses of anticoagulant therapy.
Thus, based on our observations, we recommend transesophageal echocardiography before elective surgery in all patients with persistant AF to determine the feasibility of restoring the sinus rhythm before surgery.
P5993Comprehensive characterization of experimental aortic valve stenosis by multiparametric MRI
Authors: Quast C , Zimmer S , Boenner F , Jacoby C , Gyamfi-Poku I , Piayda K , Erkens R , Niepmann S T , Adam M , Baldus S , Nickenig G , Kelm M , Floegel U 
Published: October 2019

Abstract

Background
Recently, we established an experimental model of moderate aortic valve stenosis (AS) aiming to mimic human disease progression closely. Functional and structural MRI of a mouse model in experimental aortic valve stenosis has not been accomplished so far.

Purpose
Here, we aimed at developing comprehensive MRI approach for simultaneous assessment of changes in valvular, left ventricular and aortic morphology and function.

Methods
Male 12-week-old wildtype mice (C57Bl/6) were subjected to wire injury of the aortic valve to induce aortic valve stenosis. High resolution MRI at 9.4T was used to monitor subsequent functional and structural changes in the aortic valve, the ascending aorta, the left ventricle and aortic flow patterns.

Results
MRI permits accurate planimetry of the orifice and the thickness of the aortic valve, allows a reliable three-dimensional mapping of transvalvular aortic flow, simultaneously depicts aortic regurgitation in 3D fashion and permits assessment of left ventricular changes due to AS. In our model we observed a reduced valve orifice and an increase in valve thickness. Homogenous flow pattern under control converted to heterogenous and turbulent flow with progression of AS associated with increased aortic strain, aortic wall and left ventricular wall thickness.

Conclusions
In a murine model of aortic valve stenosis MRI is capable to reliably display a three-dimensional transvalvular aortic flow profile with concomitant quantification of structural and functional changes in aortic valve, left ventricle, and ascending aorta. This comprehensive functional imaging at high resolution and distinct reproducibility offers for the first time serial assessment of disease progression in an experimental model of aortic valve stenosis.
P5998The Phosphodiesterase 4D interacting protein averts volume overload - but not pressure overload-induced pathological myocardial remodeling
Authors: Mohamed B A , Elkenani M , Jakubiczka-Smorag J , Bader M , Hasenfuss G , Toischer K 
Published: October 2019

Abstract

Background
Although volume- and pressure-overload (VO and PO, respectively) are hemodynamic stress, each results in distinct phenotypes. The Phosphodiesterase 4D interacting protein (PDE4DIP) is a protein involved in cardiac muscle contraction and suggested to play a role in cardiomyopathy. We previously identified Pde4dip transcript as being downregulated in VO but upregulated in PO.

Objective
We wanted to address whether Pde4dip deletion would alter the progression of pathological myocardial remodeling and heart failure (HF) following hemodynamic stress.

Methods
Pde4dip knockout (Pde4dip-KO) and age- and sex-matched wild-type (WT) mice were exposed to aortocaval shunt-triggered VO or transthoracic aortic constriction (TAC)-induced PO. Mortality rates were assessed and the cardiac structure and function were determined by serial echocardiography.

Results
The PDE4DIP protein levels decreased significantly in volume-overloaded hearts. However, pressure-overloaded hearts did not alter PDE4DIP protein levels, suggesting different posttranscriptional modifications that might affect the PDE4DIP protein expression in VO versus PO. The Pde4dip-KO Hearts were structurally and functionally normal in echocardiographic and morphometric analyses. However, Pde4dip deletion mildly attenuated the mortality rates in shunt-, but not in TAC-operated mice. A significant deterioration of left ventricle geometry and function was observed in volume-overloaded WT hearts at 12 weeks after shunt, but preserved cardiac function were noticed in shunt-operated Pde4dip-KO mice. On the other hand, TAC-operated WT and Pde4dip-KO mice exhibited a significant, but comparable deterioration of cardiac structure and function compared to sham mice.

Conclusion
Here we identified the PDE4DIP as an essential regulator of pathological myocardial remodeling following VO, but irrelevant to the development of cardiac dysfunction after TAC. Further investigations are warranted to dissect the possible mechanisms underlying the protective role of PDE4DIP deletion in the setting of VO.

Acknowledgement/Funding
This work was supported by DFG (SFB1002 project D04 to KT and D01 to GH; IRTG1816 to ME); BAM was funded by DSHF
P6003Coronary artery spasm: a consequence of impaired nitric oxide/hydrogen sulphide signalling?
Authors: Liu S , Nguyen T H , Imam H , Heresztyn T , Stafford I , Chirkov Y Y , Horowitz J D 
Published: October 2019

Abstract

Background
Coronary artery spasm (CAS) represents a major cause of patient morbidity, with variable clinical response to prophylaxis with calcium antagonists and generally poor symptomatic relief with organic nitrates. The precipitation of CAS with acetylcholine may reflect impaired nitric oxide (NO) release and/or signalling. We have recently demonstrated that platelets from patients with CAS exhibit markedly impaired anti-aggregatory responses to the NO donor sodium nitroprusside (SNP) (“NO resistance”).

Purpose
In the current experiments we sought to determine whether N-acetylcysteine (NAC), which is known to potentiate haemodynamic responses to organic nitrates, reverses NO resistance in platelets from CAS patients.

Methods
Patients with CAS were studied during acute (n=11) and chronic (n=24) phases of symptoms. NAC (10 g/24 hours) was infused together with low dose NTG (2.5 μg/min) in patients presenting with acute exacerbations, and platelets were studied ex vivo. In blood samples taken from chronic CAS patients, in vitro studies were performed to evaluate the possible role of H2S release (via cysteine formation) from NAC in putative potentiation of NO effect.

Results
(1) In acute patients, NTG/NAC infusion resulted in increases in platelet response to SNP (p=0.003);
(2) In vitro studies showed that incubation with NAC or the H2S donor NaHS potentiated SNP responses (Figure 1A);
(3) Effects of NAC were reversed by co-incubation with aminooxyacetic acid (AOAA) and D, L-propargylglycine (PAG), inhibitors of enzymatic cysteine bioconversion to release H2S (Figure 1B).
Figure 1

Conclusion
CAS-associated impairment of platelet NO signaling reflects a deficiency of the H2S/NO interaction, and can be reversed using exogenous H2S donors, including NAC.
P6006Pathogenesis of symptomatic crises in patients with coronary artery spasm: evidence for acute damage to vascular glycocalyx and to circulating platelets
Authors: Nguyen T H , Liu S , Imam H , Heresztyn T , Stafford I , Chirkov Y Y , Horowitz J D 
Published: October 2019

Abstract

Background
Coronary artery spasm (CAS) is known to occur commonly even in a “pure culture”, but little is known regarding the precipitation of the symptomatic crises which characterize this disorder. There have been recent reports of the occurrence of plaque erosion and intracoronary thrombosis during CAS crises. We have recently shown that (1) the anti-aggregatory effects of nitric oxide (NO) are impaired in CAS patient and (2) release into plasma of the endothelial glycocalyx component syndecan-1 (SD-1) occurs during acute episodes of CAS, suggesting glycocalyx erosion by inflammatory enzyme release.

Objective
In the current study, we sought to determine whether this phenomenon is accompanied by damage to circulating platelets and whether activation of mast cells may represent a possible precipitant.

Methods
In patients with acute episodes and chronic phases of CAS (n=10), as well as normal subjects (n=12), plasma concentrations of SD-1, of platelet-derived microparticles (PMPs), of the mast cell enzyme tryptase and of malondialdehyde (MDA), a measure of oxidative stress, were evaluated.

Results
The results are summarized in the table. Symptomatic crises were associated with substantial elevation of SD-1 concentrations and also those of PMPs and of tryptase, relative to chronic status. However, MDA concentrations did not vary significantly during acute episodes.
Impact of acute exacerbation of CAS on markers of glycocalyx shedding (SD-1), platelet activation (PMP counts), mast cell activation (tryptase) and oxidative stress (MDA) Parameter Acute CAS Chronic CAS p* Normal subjects** SD-1 (μg/L) 50.3±3.9 14.3±4.7 <0.0001 12.7±2.4 PMPs (counts) 24200±8100 4800±1010 0.02 10400±2900 Tryptase (μg/L) 4.4±0.4 4.1±0.4 0.03 <12.0 MDA (μM) 3.2±0.2 3.1±0.1 NS 3.09±0.15 *Acute vs. chronic; **provided for reference only.

Conclusion
(1) The combination of SD-1 release and formation of PMPs suggests that CAS crises reflect both glycocalyx “shedding” and platelet activation/apoptosis, a combination which would facilitate coronary thrombosis.
(2) CAS crises are associated with mast cell activation, which may contribute to the above vascular/platelet damage.
P6147Access to essential cardiovascular medicines in Kerala, the state with the highest cardiovascular disease burden in India
Authors: Satheesh G , Puthean S , Ansil M , Unnikrishnan M K , Sharma A , Mishra S R , Jereena E 
Published: October 2019

Abstract

Introduction
The 2030 Agenda for Sustainable Development has prioritized the reduction of premature mortality due to NCDs – including cardiovascular diseases (CVD) - by a third. To achieve this goal, countries must achieve 80% availability of affordable essential medicines. Essential medicines as identified by the World Health Organization are those that meet the priority healthcare needs of majority population. Globally, India has the second highest CVD burden with over 1.7 million deaths annually, with the highest CVD morbidity and mortality rate in Kerala.

Purpose
To evaluate the availability, prices and affordability of essential CVD medicines in Kerala state to facilitate implementation of informed public health policy.

Methods
Using WHO/HAI methodology, we obtained data on availability and prices for 25 essential CVD medicines in a representative sample of 7 public-sector hospitals (survey anchors) and 37 private retail pharmacies located near the survey anchors in four districts. Additionally, we obtained the data from 10 government-subsidized discount pharmacies. We report availability as percentage of surveyed facilities where a given medicine was found. Median prices ratios (MPRs) were calculated by comparing consumer prices to the MSH International Reference Prices (IRPs). Medicines were considered affordable if the monthly supply costs less than one-day's wage of the lowest paid government worker.

Results
In the public-sector facilities (hospital and discount pharmacies combined), the mean (SD) availability of the surveyed CVD medicines was 52% (35.3%) for generic and 35.3% (20.7%) for originator brand (OB) version. 28% of surveyed medicines (including amlodipine, clopidogrel, losartan, metformin) were available in over 80% pharmacies. 12% (captopril, streptokinase and glyceryl trinitrate) were not available in any of the facilities.
In the private sector, mean (SD) availability of generic and OB versions was 64.4% (37.2%) and 43.7% (34.6%), respectively. MPR was 1.28 [range: 0.02 (insulin NPH) – 16.7 (simvastatin)] for both lowest-priced generics (LPG) and most-sold generics (MSG). The lowest paid government worker in Kerala would spend 0.06 - 3.48 days' wages for the monthly supply of essential CVD medicines in the private sector.
In government-subsidized discount pharmacies, mean availability was 49.3%. The generic medicine prices were 74% lower than in the private sector.

Conclusions
Availability of essential CVD medications in both public and private sector pharmacies fall short of the 80% target. In the private-sector, many essential CVD medications seem unaffordable especially considering the polypharmacy among CVD patients. Introducing policies to improve medicine availability in government-subsidized discount pharmacies is crucial in tackling Kerala's ever-increasing CVD burden.
P6153High risk plaque by coronary CTA predict cardiac events but not all-cause mortality: long term follow up
Authors: Senoner T , Plank F , Babieri F , Dichtl W , Beyer C , Friedrich G , Feuchtner G M 
Published: October 2019

Abstract

Background
Ultra long-term (10 years) outcome data of coronary computed tomography angiography (CTA) for coronary heart disease (CHD) screening are lacking. Novel CTA imaging biomarkers (“high-risk-plaque”) may improve risk stratification.

Aims
To define CT-imaging predictors for long–term outcomes.

Methods
1430 low-to-intermediate-risk patients (mean age 57.9 years; 44.4% females) were included into our prospective cohort study. Coronary Calcium Score (CCS) and CTA were performed. CTA was evaluated for: Stenosis severity (minimal<25%; mild<50%; moderate 50–70%; severe >70%) (CADRADS 1–4), total mixed plaque burden (G-score), high–risk-plaque criteria: 1) low attenuation plaque 2) Napkin-ring (“lunar-eclipse” sign) 3) spotty calcification 4) remodeling index
Primary endpoint was all-cause mortality, secondary endpoints cardiovascular mortality and composite (non-fatal and fatal) MACE.

Results
Over a follow-up of mean 10.55 years ±1.98 (range, 6.1–12.8), all-cause mortality rate was 106 (7.4%), cardiovascular mortality 25 (1.75%) and composite MACE 57 (4%).
In patients with negative CTA, cardiovascular mortality was 0% and composite MACE rate 0.2%.
Stenosis severity (CADRADS) was the strongest predictor for all 3 endpoints (p<0.001) on multivariate analysis (unadjusted and adjusted for risk factors, p<0.001) but calcium score >100 AU only predicted mortality on the unadjusted multivariate analysis (p=0.045) but not on the adjusted.
On multivariate analysis, G-score (p<0.0001), LAP<60HU and the Napkin-Ring predicted composite MACE (p<0.001) but not all-cause mortality, before and after adjusting for risk factors (p=0.007 and 0.001 for LAP<60HU and Napkin-Ring, respectively) while spotty calcification and remodeling index did not. 465 had calcium score zero and in 156 (33.5%) of those, noncalcified fibroatheroma were found (total rate, 11%), 4.9% had >50% stenosis. However only 1 patient with calcium score zero died while there were 6 MACE.
High risk plaque with “lunar eclipse”

Conclusions
Long-term prognosis is excellent if CTA is negative. Stenosis severity by CTA predicts all-cause and cardiovascular mortality, while calcium score predicts only mortality. Plaque burden and the high-risk plaque criteria LAP<60 and Napkin-Ring (syn. “lunar eclipse”) are strong predictors of MACE, but not all–cause mortality. Coronary CTA outperforms calcium scoring for risk stratification.