bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracorporeal cardiopulmonary resuscitation: a national study on the association between survival and biomarkers of hypoperfusion, inflammation, and organ failure
Authors: Gregers E , Moerk S R , Linde L , Andreasen J B , Smerup M , Kjaergaard J , Moeller-Soerensen P H , Holmvang L , Christensen S , Terkelsen C J , Moeller J E , Lassen J F , Rieber L P , Laugesen H , Soeholm H 
Published: October 2022

Abstract

Background
In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR).

Purpose
We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR.

Methods
This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011–2020). Biomarkers at admission and consecutively two days after ECPR initiation were retrieved. Odds ratio (OR) of 90-day survival were assessed by logistic regression analyses. Cut-off values were calculated from area under the curve (AUC) via the Youden index.

Results
Fifty-six patients (25%) survived to hospital discharge, all were still alive after 90-days and 91% had a favorable neurological status at discharge. Factors independently associated with 90-day survival were: male sex, shockable presenting rhythm, low flow time, platelets, pH, lactate, C-reactive protein, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and creatine kinase MB (CK-MB) level. Comparing the ability of standard predictive variables (age, sex, shockable presenting rhythm, witnessed arrest, and low flow time) and selected biomarkers (from multivariate analyses) in predicting 90-day survival, biomarkers day 2 after OHCA were significantly better than standard variables (AUC 0.79 vs. 0.56, p=0.01).

Conclusion
Biomarkers of hypoperfusion (low lactate and high pH), inflammation (high platelets and CRP), and organ failure (low LDH, ALP, and CK-MB) were independently associated with 90-day survival. Biomarkers on day 2 after OHCA (d-dimer, ALP, and CK-MB) were more predictive of 90-day survival than standard predictive variables.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Odense University Hospital's and Rigshospitalet's Common Research Foundation
Selection of patients for mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study
Authors: Linde L , Moerk S R , Gregers E , Andreasen J B , Lassen J F , Ravn H B , Schmidt H , Riber L P , Laugesen H , Terkelsen C J , Moeller-Soerensen P H , Holmvang L , Kjaergaard J , Hassager C , Moeller J E 
Published: October 2022

Abstract

Background
Extracorporeal cardiopulmonary resuscitation (ECPR) is a potential salvage therapy for selected patients with refractory out-of-hospital cardiac arrest (OHCA).

Purpose
The objective of this study was to describe the characteristics of potential ECPR patients.

Methods
This retrospective, observational cohort study included 579 patients admitted with refractory OHCA for possible ECPR at all tertiary cardiac arrest centers in Denmark between 2015 and 2020. Presenting characteristics, reasons for refraining from ECPR, and survival to hospital discharge were recorded.

Results
After initial evaluation, 221 patients (38%) proceeded to ECPR, and 358 (62%) were considered futile. Median prehospital low-flow time was 70 minutes [interquartile range 56–85] in ECPR patients and 62 minutes [48–81] in no-ECPR patients, p&lt;0.001. Intra arrest transport was more than 50 km in 92 (42%) ECPR patients and 135 in no-ECPR patients (38%), p=0.25. Treatment decision was taken by a team of three specialists in 513 cases (97%). The leading cause for not initiating ECPR was duration of low flow time (39%). Severe metabolic derangement and low end-tidal CO2 (ETCO2) were contributing factors in 35% and 31%, respectively, Figure 1. 83% of the patients had two or more contributing factors recorded as reasons for not initiating ECPR, Figure 2. The most prevailing combination of contributing factors were non-shockable rhythm, low ETCO2, and metabolic derangement or duration of prehospital low flow time combined with low ETCO2. Survival to discharge was achieved in six patients (1.7%) in the no-ECPR group and 50 (23%) in the ECPR group.

Conclusions
In this large nationwide study of patients admitted for possible ECPR, 62% were not treated with ECPR. The most frequent reasons to abstain from ECPR were duration of prehospital low flow time, metabolic derangement, and low ETCO2.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation
Relationship between left ventriculoarterial coupling and damage stage in severe aortic stenosis
Authors: Migliore R A , Adaniya M E , Barranco M A , Gonzalez S , Dorsch J 
Published: October 2022

Abstract

Background
In patients with severe aortic stenosis (AS), an anatomic and functional staging classification has been proposed to assess extent of cardiac chambers damage to improve the decision of aortic valve replacement based only in symptoms or ejection fraction (EF) &lt;50%. This staging relies on the concept that left ventricular (LV) afterload secondary to AS induce LV dysfunction with progression to LV and right ventricular damage. However, afterload has valvular and vascular components, and the latter is not evaluated by the classification of stages. Characteristics of arterial vasculature can impact on LV function through the alteration in LV-VA coupling which is the relationship between effective arterial elastance (Ea) and LV end-systolic elastance (Emax).

Objective
To evaluate the relationship between LV-VA coupling and the different stages of cardiac damage in severe AS.

Methods
We studied 205 patients, age average 70±11 years, 117 men, with severe AS (AVA &lt;1 cm2) with Doppler echocardiography. Measurements of cardiac chambers were made according to ASE/EACVI Guidelines. Ea was calculated as end-systolic pressure divided by stroke volume. End-systolic pressure was obtained from tonometry of carotid pulse. Emax was estimated by the method of Senzaki (1) as an index of LV contractility. Ea / Emax ratio was used to assess LV-VA coupling. Patients were divided in five groups according to the classification of staging cardiac damage proposed by Tasted (2): stage 0, no valvular cardiac damage; stage 1, LV damage (EF &lt;60%); stage 2, left atrial or mitral valve damage; stage 3, pulmonary vasculature or tricuspid valve damage and stage 4, right ventricular damage, or subclinical heart failure (LV stroke volume index &lt;30 ml/m2).

Results
Mean ± standard deviation (see Table 1). No patient was in stage 0. Symptoms was present in 40% of stage 1, 85% of stage 2 and 100% of stage 3 and 4. Ea increases from stage 2 to stage 4 while Emax did not change in those groups but decreased from stage 1 to 2. Consequently, LV-VA coupling progressively decreased from stage 1 to 4.

Conclusions
Worsening of LV-VA coupling increase with staging cardiac damage. The alteration of LV-VA coupling from stage 2 to 4 is due to an increase in Ea without significant changes in level of contractility (Emax). The progression of cardiac damage appears to be related not only to valve disease but also to the characteristics of arterial vasculature.

Funding Acknowledgement
Type of funding sources: None.
The impact of atrial fibrillation on prognosis in aortic stenosis
Authors: Laenens D , Stassen J , Galloo X , Ewe S H , Singh G K , Amanullah M R , Hirasawa K , Sia C H , Butcher S C , Chew N W S , Kong W K F , Poh K K , Ding Z P , Ajmone Marsan N , Bax J J 
Published: October 2022

Abstract

Background
Atrial fibrillation (AF) and aortic stenosis (AS) are both highly prevalent and increasing with age. Various studies have focused on the complex relationship between these entities that frequently coexist. AS might induce adverse cardiac remodelling, which is associated with poor prognosis in severe AS. Left atrial remodelling, especially left atrial enlargement, is also an important risk factor for AF.

Purpose
To evaluate the additive prognostic value of AF besides markers of left atrial and left ventricular remodelling in patients with AS, irrespective of severity of AS and left ventricular ejection fraction (LVEF).

Methods
Patients with moderate and severe AS were selected and history of AF was assessed. Subgroups were defined according to LVEF (reduced (&lt;50%) vs. preserved (≥50%)) and severity of AS (moderate vs. severe). The endpoint was all-cause mortality. Unadjusted Kaplan-Meier survival curves were plotted. Four multivariable Cox regression models were constructed.

Results
In total, 2849 patients with moderate and severe AS (mean age 72±12 years, 54.7% men) were evaluated of whom 686 (24.1%) had a history of AF. Regarding the defined subgroups, 1091 (38.3%) patients had severe AS and 2207 (77.5%) patients had preserved LVEF. During a median follow-up time of 60 months (interquartile range 30 to 97), 1182 (41.5%) patients died. Ten-year mortality rate in patients with AF was 46.8% compared with 36.8% in patients with sinus rhythm (SR) (Figure 1) (p&lt;0.001). In subgroup analysis, patients with AF and severe AS, moderate AS or preserved LVEF had worse survival than those who maintained SR (p=0.015, p&lt;0.001 and p&lt;0.001 respectively). On univariable (HR: 1.42; 95% CI: 1.25 to 1.62; p&lt;0.001) and multivariable Cox regression analysis (HR: 1.19; 95% CI: 1.02 to 1.38; p=0.026) adjusting for age, body mass index, hypertension, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, kidney function, New York Heart Association class, aortic valve replacement as a time-dependent covariate, left ventricular mass index, left ventricular end-diastolic volume index, LVEF, mean aortic valve gradient, tricuspid annular plane systolic excursion, AF is independently associated with mortality (Table 1; model 1). However, when correcting for LAVI, E/e' or both, AF is no longer independently associated with all-cause mortality (Table 1; model 2–4).

Conclusion
Patients with moderate or severe AS and AF have a significantly higher 10-year mortality rate than patients with SR. This finding is irrespective of AS severity and also apparent in the subgroup with preserved LVEF. Nonetheless, when correcting for markers of diastolic dysfunction, AF is not independently associated with outcome in patients with moderate or severe AS.

Funding Acknowledgement
Type of funding sources: None.
The burden of coronary revascularization associated with lipoprotein(a) in patients with atherosclerotic cardiovascular disease: data from the UK Biobank
Authors: Welsh P , Byrne H , Costa-Scharplatz M , Fonseca A F , Itani T , Farries G , Zabiby A A , Narasimham S , Martin L , Sattar N 
Published: October 2022

Abstract

Background/Introduction
Elevated lipoprotein(a) [Lp(a)] is an inherited, independent, and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). In a previous analysis of 30,510 ASCVD patients from UK Biobank, adjusted models showed a 100 nmol/L (≈50 mg/dL) difference in Lp(a) was associated with a 19% (95% CI 14–23%) higher risk of coronary revascularization (Welsh P, 2022).

Purpose
To determine the absolute risk for coronary revascularization in an ASCVD population with elevated versus normal Lp(a) levels.

Methods
This was an observational, retrospective study including 32,537 patients from UK Biobank with an ASCVD diagnosis (CHD, cerebrovascular or peripheral arterial disease). Absolute risk (AR) of coronary revascularization (number of coronary revascularizations per 100-person-years) was reported in patients with normal (&lt;65 nmol/L ≈ 30 mg/dL; n=22,257) and elevated (≥150 nmol/L ≈ 70 mg/dL; n=5,204) Lp(a) levels across two time periods: within the first year of ASCVD diagnosis, and using all available follow-up data (median 4.7 years). Lp(a) was measured in an accredited single laboratory using a method standardized to WHO/IFCC reference material. The AR was also calculated for various subgroups within the ASCVD population.

Results
Within the first year after ASCVD diagnosis, 628 (12.07%) of the population with elevated Lp(a) underwent coronary revascularization compared to 1,787 (8.03%) with normal Lp(a). Those with elevated Lp(a) had a higher AR (14.00 per 100-person-years, 95% CI 13.02–14.99; p&lt;0.001) than those with normal Lp(a) (9.34; 95% CI 8.92–9.76). This also held in a subgroup with myocardial infarction (MI; n=9,588), AR of 18.98 (95% CI 16.95–21.01) in those with elevated Lp(a) (n=1,571) vs. AR of 13.02 (95% CI 12.16–13.89) in those with normal Lp(a) (n=6,441) (p&lt;0.001). AR of coronary revascularization within the first year of ASCVD diagnosis was also greater in participants with family history of CV disease (p&lt;0.001) and premature CV disease (&lt;60 years of age) (p&lt;0.001). When using all available follow-up, AR of coronary revascularization was higher in participants with elevated versus normal Lp(a) in the ASCVD population (3.79 vs 2.55; p&lt;0.001) and across all subgroups.

Conclusion
Elevated Lp(a) in patients with ASCVD was associated with increased risk of coronary revascularization in the first year (and subsequently), including those with a prior MI, premature CV disease, or family history of CV disease. Lp(a) testing in ASCVD patients can therefore aid estimations for the risk of revascularization, and thus the targeting of additional therapies to lower such risks.

Funding Acknowledgement
Type of funding sources: None.
Exercise-induced ventricular arrythmia in asymptomatic patients with Mitral Valve Prolapse
Authors: Wallet T , Al Mohani A , Waintraub X , Berman E , Mertens E , Bouziri N , Allali Y , Helft G , Lefeuvre C , Isnard R , Montalescot G , Hammoudi N 
Published: October 2022

Abstract

Introduction
Mitral Valve Prolapse (MVP) is associated with complex ventricular arrythmia (VA) and sudden cardiac death but risk stratification remains unclear. Exercise induces an hyperadrenergic state and could trigger VA, however, data on exercise-induced VA (EIVA) in MVP patients are scarce.

Objective
To describe EIVA prevalence, origin, characteristics and associated features in MVP patients.

Methods
In this observational prospective study, 64 MVP asymptomatic patients (58±14 years, 41 men) with mild to severe mitral regurgitation (MR) and without left ventricular (LV) dysfunction, underwent echocardiography and symptom-limited exercise testing. Continuous 12-lead ECG monitoring was performed throughout testing. Severe EIVA was defined as ventricular triplets, sustained or non-sustained ventricular tachycardia (NSVT) or ventricular fibrillation.

Results
All patients exercised at maximal intensity until exhaustion. EIVA was observed in 54 (84%) subjects including 12 (19%) patients with severe EIVA (7 triplets, 5 NSVT). Severe EIVA originated mainly from the mitral apparatus (all but one) and occurred at high exercise intensity (median 90% of predicted workload) or during early recovery phase.
Compared to the rest of the cohort the patients with severe EIVA had similar resting ECG characteristics, similar LV dimension and function, similar degree of MR and mitral apparatus morphology. Finally, severe EIVA was not associated with an alteration of exercise tolerance.

Conclusion
Exercise frequently unmasks ventricular arrythmia in patients with MVP. EIVA appears not linked to MVP features nor to exercise tolerance and seems to provide additional phenotyping information that could be linked to prognosis.

Funding Acknowledgement
Type of funding sources: None.
Left atrial function may mitigate the effect of mitral regurgitation on right chambers in patients with severe aortic valve stenosis
Authors: Urbani G , Springhetti P , Quer L , Dotto A , Ciceri L , Fanti D , Maffeis C , Tafciu E , Bergamini C , Nistri S , Inciardi R M , Ribichini F L , Benfari G 
Published: October 2022

Abstract

Introduction
Left atrial (LA) function has been associated to right chambers hemodynamics in the context of mitral valve regurgitation (MR). However, this physiological interplay between left atrial function, mitral regurgitation and right ventricular (RV) parameters has not yet been clarified in patients with aortic valve stenosis (AS).

Aim of the study
To assess the combination of LA function and different MR grades with right chambers performance and pulmonary non-invasive hemodynamics status in patients with severe AS using an advanced automated echocardiographic approach.

Methods
Consecutive patients with severe AS referred to our institution were analyzed. Mitral regurgitation was classified according to integrative guideline-based criteria. 2D advanced speckle tracking echocardiography analysis was conducted to measure the LA peak atrial longitudinal strain (PALS) and right ventricular free wall strain, (RVFWS) using Tomtec Arena, version TTA2 41.00, with dedicated LV/LA/RV analysis option (Tomtec, Unterschlei heim, Germany). All conventional right chambers performance indexes were also measured: TAPSE, S'- TDI, fractional area change, systolic pulmonary artery pressure (sPAP). We featured 3 patients groups based on MR grade and LA function: (a) no/mild MR and preserved PALS (above the median); (c) &gt;mild MR and reduced PALS; (b) the remaining patients with &gt;mild MR and low PALS or &gt;mild MR and high PALS.

Results
A total of 102 patients with severe aortic stenosis formed the study cohort: age was 82±9, 47% were female, mean left-ventricular-ejection-fraction 56%±12, more than mild MR was present in 24% of patients, mean PALS was 19±10%, sPAP 38±12 mmHg, RVFW strain 21±6%, and RVFW/sPAP 0.62±0.25. The 3 subgroups presented similar age and sex distribution. Right ventricular function significantly worsened moving from group (a) to (c); RVFW strain decreased from 25±5 (a) to 19±7 (b) and 17±5% (c), p&lt;0.001; sPAP increased from 34±9 (a) to 39±12 (b) and 47±13 mmhg (c), p&lt;0.001; and RVFW/sPAP decreased from 0.76±0.21 (a) to 0.54±0.23 (b) and 0.39±0.11 (c), p&lt;0.001. Patients in the group (c) were more symptomatic (NYHA class III/IV increase from 40% in group a and 63% in group (b) to 80% in group c, p=0.006). When added to MR grade, in a logistic regression analysis, PALS provided incremental prediction of all right ventricular parameters (p&lt;0.01).

Conclusion
This study highlights that the combination of MR and reduced LA function is associated with symptoms and RV impairment in patients with severe AS. These preliminary results suggest that preserved LA function may modulate the adverse effects of the AS-MR combination by preventing/delaying the development of pulmonary hypertension and right ventricular dysfunction.

Funding Acknowledgement
Type of funding sources: None.
Subvalvular aortic stenosis and patent ductus arteriosus: a not so rare combination
Authors: Gonzalez Velasquez P J , Ruiz-Esparza Duenas M E , Arias-Godinez J A 
Published: October 2022

Abstract

Background
The combination of subvalvular aortic stenosis and patent ductus arteriosus (PDA) has been described as rare. We present the largest case series of adult patients with this combination.

Purpose
To describe the prevalence and echocardiographic characteristics of subvalvular aortic stenosis in PDA adult patients in a 20-year period.

Methods
7512 patients with PDA, 791 adults. We found 60 patients with subvalvular aortic stenosis and PDA and compare them with a 60 randomly selected PDA alone patients control group.

Results
The prevalence of subvalvular aortic stenosis in PDA patients was 7.5%. This combination was more frequent in women (71%), median age at diagnosis was 26 years. 45% had a third congenital heart condition (ventricular septal defect was the most frequent). 88% underwent PDA closure. Comprehensive echocardiography was performed in all patients, we found that patients with the combination of subvalvular aortic stenosis and PDA had larger left ventricle (LV) mass index (95 vs 79 g/m2, p 0.02), higher frequency of concentric LV hypertrophy (23 vs 10%, p 0.05) and higher LV ejection fraction (62 vs 58%, p&lt;0.01) than PDA alone patients. Right ventricle (RV) enlargement (20 vs 11%, p 0.04) and a high echocardiographic probability of pulmonary hypertension (11 vs 2%, p 0.02) were more frequent in PDA alone patients. At long term post surgical correction follow-up, 73% of patients in the subvalvular aortic stenosis and PDA group developed a significant (at least moderate) valvular heart condition, specially aortic regurgitation (38 vs 10%, p&lt;0.01). In a logistic regression model, subvalvular aortic stenosis was associated with developing at least moderate valvular heart disease at follow-up (OR 3.27 CI 1.44–7.39, p&lt;0.01).

Conclusion
The combination of subvalvular aortic stenosis and PDA is not rare. This patients have larger LV mass, higher frequency of concentric LV hypertrophy and develop less pulmonary hypertension and RV enlargement than patients with PDA alone. The coexistence of subvalvular aortic stenosis is associated with long term post closure development of significant valvular heart disease in PDA patients.

Funding Acknowledgement
Type of funding sources: None.
Improved diagnostic accuracy for apical hypertrophic cardiomyopathy
Authors: Hughes R K , Shiwani H , Rosmini S , Burke L , Pierce I , Castelletti S , Xue H , Kellman P , Lopes L R , Treibel T , Manisty C , Captur G , Davies R , Moon J 
Published: October 2022

Abstract

Introduction
The diagnosis of apical hypertrophic cardiomyopathy (ApHCM) is contingent on demonstrating apical maximum wall thickness (MWT) of ≥15mm; the same threshold as other HCM subtypes. However, the myocardium naturally tapers towards the apex in healthy individuals, so ≥15mm MWT is proportionately higher in the apex than in naturally thicker basal segments. Using cardiac magnetic resonance (CMR), relative ApHCM has been described (typical ECG features, loss of apical tapering, cavity obliteration but hypertrophy &lt;15mm). Wall thickness measurement using machine learning now exceeds human performance.

Purpose
We aimed to redefine the optimal diagnostic threshold for ApHCM using segment-specific criteria based on a large cohort of healthy control subjects.

Methods
Segmental wall thickness was measured using healthy subjects from the UK Biobank using a clinically validated machine learning algorithm1,2. A normative reference range was established for all 16 segments, conditioned to body surface area (BSA), sex and age. Derived segment-specific wall thickness thresholds were used to define optimal disease thresholds for patients clinically managed with overt (MWT ≥15mm) and relative ApHCM (MWT &lt;15mm, but typical ECG and imaging findings).

Results
4118 UK biobank subjects were used to define normal segmental thicknesses and reference ranges. These were applied to ApHCM (73 overt, 31 relative). There were no apical wall thickness age related differences. The upper limit of the 95% confidence interval corresponded to a combined maximum apical MWT for both males and females of 10.4mm using non-indexed measurement, or 5.6mm/m2 when indexed to BSA. Non-indexed segmental threshold identified 100% of ApHCM patients (true positives), 81% (25 of 31) relative ApHCM and 3% (115 of 4118) of healthy UK biobank subjects (false positives). Indexed segmental thresholds improved the diagnostic potential in relative ApHCM without an increase in false positives (100% of ApHCM patients, 84% (26 of 31) of relative ApHCM patients, and 3% healthy UK biobank (127 of 4118).

Conclusion
We propose new diagnostic criteria for ApHCM using segmental indexed apical wall thickness of &gt;5.6 mm/m2 to better identify inappropriate apical hypertrophy in those whose wall thickness does not meet current criteria for diagnosis.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation