bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial retargeting of AAV9 in vivo
Authors: Bozoglu T , Lee S , Ziegler T , Kupatt C 
Published: October 2022

Abstract

Background
Adeno-associated virus (AAV) is favorable choice for gene transfer and gene editing applications in vivo, due to its low integration rate and low immunogenicity, as well as a variety of natural and engineered serotypes providing different tissue and cell type tropism. Endothelial cells, however, are remarkably resistant to transduction by AAVs.

Purpose
The aim of this study is to retarget wild type AAV9 vectors using a combination of polyamidoamine dendrimers (PAMAM) and peptides with endothelial affinity.

Methods
An endothelial-affine peptide sequence was obtained via bio-panning of a phage display library on endothelial culture cells. Second-generation PAMAM dendrimers were linked to the peptide via PEG linker. AAV9 vectors were coated with these modified dendrimers (G2CNN) immediately before in vivo applications.

Results
mTmG-mice or mTmG-pigs were utilized as reporter organisms, where red-to green fluorescence change upon Cre expression displays cellular resolution of transduction. Cre encoding AAV coated with G2CNN application systemically (mice) or locally (pigs) transduced over 30% of CD31+ cells in skeletal muscle and heart.
Functional relevance of endothelial retargeting was assessed by systemic injections of G2CNN coated AAV9 encoding for three transgenes:
1) An artificial adhesion molecule (S1FG). In wild type mice, S1FG expression in endothelial cells increased leukocyte adhesion in cremaster muscle vasculature (day 10 post injection).
2) Anti-inflammatory Annexin A1 (Anxa1). In ApoE−/− mice on high-fat diet, Anxa1 expression reduced long term leukocyte recruitment in carotid artery (day 28 post injection).
3) sgRNA targeting the vasodilatory enzyme eNOS (endothelial nitric oxide synthase). In conditional Cas9 transgenic mice, editing of eNOS via AAV delivered Cre and sgRNA caused increase of blood pressure (day 56 post injection).

Conclusion
Endothelial retargeted AAV9 efficiently transduced endothelial cells of skeletal muscle and heart in vivo. Accordingly, in vascular and atherosclerosis models, these modified vectors may enable gene transfer.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Bundesministerium für Bildung und ForschungDeutsche Forschungsgemeinschaft
Prognostic value of PET derived coronary flow reserve: should we correct for resting perfusion product?
Authors: Ahmed A I , Saad J M , Alahdab F , Han Y , Alfawara M , Nabi F , Mahmarian J , Al-Mallah M H 
Published: October 2022

Abstract

Introduction
Positron emission tomography (PET) myocardial perfusion imaging (MPI) derived coronary flow reserve (CFR) is an important risk-stratifying tool to tailor management of patients with coronary artery disease. Resting myocardial blood flow (MBF) is positively correlated to the product of resting heart rate and systolic blood product (resting pressure product – RPP), and can in turn lead to lower CFR in the setting of normal stress MBF.

Purpose
We aimed to assess the comparative incremental prognostic value of uncorrected to RPP-corrected CFR in predicting incident events.

Methods
Consecutive patients who had clinically indicated PET MPI were included. Patients were followed from the date of imaging to incident major adverse cardiovascular event (MACE: inclusive of all-cause death, myocardial infarction, admission for heart failure and late revascularization – percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) &gt;90 days after imaging).

Results
The study population consisted of 2,893 patients with clinically indicated PET MPI (mean age 67 (±12), 53% male, 41% Caucasian). Cardiovascular risk factors were prevalent (88% hypertensive, 80% dyslipidemic, 47% diabetics, 18% ever smoking). After a mean follow-up of 8±7 months, 250 patients (8.6%, 10.7 per 1000 person-year) experienced MACE (90 D/38 MI/51 PCI/11 CABG/113 HF). Both uncorrected and corrected CFR were independently associated with incident MACE (HR 0.38, 95% CI 0.29–0.51, p&lt;0.001 and 0.61, 95% CI 0.50–0.76, p&lt;0.001 respectively). A comparison of model incremental prognostic value showed the model with uncorrected CFR had a statistically higher Harrell's C (0.76 vs 0.77, p=0.23).

Conclusion
Our findings showed that the prognostic value of CFR was preserved even in the setting of high resting blood pressure or heart rate. This suggests that correction for RPP should be selective.

Funding Acknowledgement
Type of funding sources: None.
Problem of implicit assumptions about left ventricular geometry in the calculation of myocardial mass by echocardiography – a validation study with cardiac magnetic resonance
Authors: Winkler A , Sveric K , Doering C , Mierke J , Svitil J , Heidrich F M , Linke A , Ulbrich S 
Published: October 2022

Abstract

Background/Introduction
Cardiac magnetic resonance imaging (CMR) is regarded as the reference method in assessing left ventricular (LV) myocardial mass. However, 2-dimensional echocardiography (Echo) is still used due to availability and practicability.

Purpose
We sought to assess measurements of LV myocardial mass from Echo exams and validate the results with CMR on a large cohort of patients.

Methods
We analyzed 357 patients who underwent clinically indicated CMR examinations and performed a standard Echo at the same day. In Echo, the commonly used Devereux formula (CUBE) was assessed for the calculation of LV mass: 0.8 × {1.04 × [([LV end-diastolic diameter + diastolic septum-thickness + posterior wall-thickness]3 − LV end-diastolic diameter3)]} + 0.6. Mass was indexed on body surface area (g/m2). Correlation (r), regression (R2) and Bland-Altman analysis were performed in order to assess bias between the two methods. Significance was defined as a 2-tailed P value &lt;0.05.

Results
LV myocardial mass was measured in 345 patients with CMR and Echo. The median age was 61 years [19–79], 44% were female and CMR was performed due to coronary artery diseases (45%), suspected or florid myocarditis (31%) or further diagnosis of non-ischemic heart failure (24%). LV ejection fraction (EF) ranged between 13 and 71%. We found a significant relation of measurements for myocardial mass between Echo and CMR (R2=0.6, p&lt;0.001) (Figure 1, left). However, there was a significant proportional bias (R2=0.47, p&lt;0.001) depending in the amount of LV mass measured (Figure 1, right). As expected, the measurement bias correlated not only with the amount of mean wall-thickness (septum & posterior wall) from Echo, but also with LV end-diastolic diameter (r=−0.55 and −0.41, p&lt;0.001 for all). Interestingly, the amount of LV EF correlated reversely with the proportional bias (r=0.34, p&lt;0.001).

Conclusion
The results provided by our study, highlight the problem of implicit assumptions of LV geometry in the calculation of LV myocardial mass by Echo (CUBE) compared to CMR. Furthermore, the strongly biased differences between these two measurement methods are not negligible and warrant further investigation.

Funding Acknowledgement
Type of funding sources: None.
Feasibility and role of echocontrast evaluation of patients with LVAD
Authors: Dellino C , Pergola V , Baroni G , Semeraro L , Mastro F , Arura P , Cecchetto A , Previtero M , Tarzia V , Mele D , Gerosa G , Iliceto S 
Published: October 2022

Abstract

Background
Advanced heart failure is a clinical syndrome characterized by persistent or progressive symptoms of heart failure despite optimal medical therapy. Left ventricular assist device (LVAD) brings survival benefits and improvement in quality of life, compared with conventional medical treatments. Development of Right ventricle failure in patients with LVAD has a direct effect on mortality and hospitalization.

Purpose
Evaluation of clinical safety and feasibility of echocontrast in patients implanted with 3 different types of LVAD; improvement in the visualization of heart structures; intra and inter-operator agreement of RV assesement with and without contrast.

Methods
43 patients were implanted with LVAD, 7 patients (16%) with Jarvik 2000, 31 (72%) with HeartMAte 3, 5 (12%) with (HeartWAre HVAD). Nine patients (21%) had contraindication or refused contrast. In 3 (7%) patients was technically challenging to obtain apical images at all levels. Two (5%) patients lost their follow-up. Our final population was of 29 (67%) patients (mean age 65±7 y; 100% Male). We assessed the reproducibility of these measurements between two different expert blind operators.

Results
Total 329 (64%) of 516 RV wall segments were available for qualitative analysis without contrast vs 451 (87%) with contrast (p&lt;0.001) with a significant improvement of the evaluability of regional contractility (especially due to the better evaluation of medial and apical segments of lateral and anterior walls) and FAC (41% vs 90%, p&lt;0.001). Evaluation of TAPSE, TR and sPAP was similar with and without contrast (p=NS). All the RV parameters showed little inter-operator variability when measured with contrast. TAPSE, FAC, and RWMA showed an excellent reproducibility (ICC &gt;0.86) while it was good for 2D-baseline derived parameters (ICC = 0.74) showing improvement of inter operator reproducibility in the evaluation of regional contractility in the contrast echocardiography modality.

Conclusion
EC is safe with all the types of LVAD examined. Accurate and reproducible visualization of RV is imperative for reliability of information, a routine use of EC could play a pivotal role in interpreting RV features. EC improves RV morphologic and functional judgment allowing greater accuracy and precision in the assessment of both global and regional RV functions. This finding may have important clinical improvement, especially in the future for analysis focused in RV prognostic role in LVAD patients.

Funding Acknowledgement
Type of funding sources: None.
Accuracy of diagnostic score by echocardiography for the detection of cardiac amyloidosis in patients with proven extracardiac amyloidosis
Authors: Bauer F , Fauvel C H , Raitiere O , Si Belkacem N , Colleville B , Mulder P 
Published: October 2022

Abstract

Background
In 2021, a position statement of the ESC Working Group on Myocardial and Pericardial Diseases suggested to use an echocardiographic score (i.e., ECHO score) to confirm cardiac amyloidosis (CA) thus to avoid heart biopsy in patients with left ventricular (LV) hypertrophy &gt;12 mm and proven extracardiac amyloidosis.

Purpose
To test the accuracy of ECHO-score in a broad spectrum of patients with proven cardiac amyloidosis and anatomical LV hypertrophy measured by echocardiography.

Methods
One hundred and twenty patients with proven CA (both from ATTR and AL forms) underwent comprehensive echocardiography including parietal wall thickness (+3 points), Doppler E/e' ratio (+1 point), TAPSE (+2 points), LV global longitudinal strain (1 point) and systolic longitudinal strain apex to base ratio (+3 points) and compared to 13 controls. A score ≥8 points in the presence of LV wall &gt;12 mm which predicts CA, was investigated in patients with LV hypertrophy from 12.1 to 15.0 mm, from 15.1 to 20 mm and over 20 mm. Cardiovascular magnetic resonance (CMR) imaging was available in 63 patients for extracellular volume measurement &gt;0.40% and diffuse late gadolinium enhancement assessment, both present to confirmed amyloidosis.

Results
ATTR and AL amyloidosis accounted for 77% and 23%, respectively. Age averaged 76±7yo and 72% of patients were male. LV ejection fraction averaged 61±5%. The ECHO score averaged 6.4±2.5 in patients with LV hypertrophy from 12.1 to 15.0 mm (n=29), 7.9±2.6 in patients with LV hypertrophy from 15.1 to 20.0 mm (n=59) and 9.8±1.7 when LV hypertrophy was &gt;20 mm (n=32). Figure 1 depicts the sensitivity of ECHO score alone and in addition to CMR as a function of LV hypertrophy range. In patients with LV hypertrophy &gt;20 mm, ECHO score alone has a sensitivity near 100% and CMR is useless to confirm cardiac amyloidosis. Between 15.1 to 20.0 mm of hypertrophy, both ECHO and CMR are necessary to reach a sensitivity of 100%. Unfortunately, below 15 mm of LV hypertrophy, neither ECHO nor CMR altogether predict cardiac amyloidosis with good accuracy, meaning heart biopsy is still useful.

Conclusion
Upon the degree of LV hypertrophy in a patient with extrcardiac amyloidosis, ECHO score alone or in combination with MRI are efficient only if myocardial parietal thickness is above 15 mm.

Funding Acknowledgement
Type of funding sources: None.
Prognostic implications of biventricular and left radial strain in heart failure
Authors: Matshela M R 
Published: October 2022

Abstract

Background
Chronic heart failure (CHF) is associated with the high ventricular filling pressures with subsequent negative impact on the left (LV) and right ventricular (RV), and left atrium (LA) mechanics, and pulmonary vasculature. All these could lead to poor long-term outcome.

Purpose
Assess the prognostic implications of LA, LV and RV mechanical dysfunction, and pulmonary hypertension, in CHF based on advanced echocardiographic technology.

Methods
A total of 2110 CHF patients were retrospectively reviewed and enrolled for the analyses. The 2D-Speckle tracking echocardiographic analysis was used to measure the peak LV, RV and LA longitudinal strain. The long-term outcomes were evaluated for all-cause CVS outcomes and recurrent hospitalization.

Results
For the 941eligible patients [mean age: 61±4; 62% male sex], 244 reached the combined endpoint. Population was divided into three groups based on the mean pulmonary artery systolic pressure (mPASP): Group 1, 25&lt;mPASP≤40 mmHg; Group 2, 40&lt;mPASP≤55 mmHg and Group 3, &gt;mPASP 55 mmHg. Mean follow-up was 2.5±0.6 years. The higher mPASP was demonstrated in those with higher left atrial volume ndex (LAVI), NYHA ≥II class, pulmonary diseases, presence of at least moderate mitral and/or tricuspid regurgitation (TR) grades, significantly lower LVEF, lower strain values (LA, LV, RV), and tricuspid annular plane systolic excursion (TAPSE), p&lt;0.001). High mPASP, lower LVEF and RV dysfunction were independent predictors of survival after multiple adjustments using different models.

Conclusions
Multiple factors are associated with poor outcomes in CHF; particularly the presence of RV dysfunction, severe PH and severely impaired, which would guide further manage of CHF and to consider other treatment options including device therapy or even transplantation. All these factors could strongly influence the risk stratification of patients with CHF

Funding Acknowledgement
Type of funding sources: None.
Impact of atrial fibrillation on outcome of percutaneous mitral valve repair (PMVR) procedure
Authors: Mohrez Y , Strohmaier J , Paiva T C , Forkmann M , Butz S , Acil T , Schnupp S , Mahnkopf C , Busch S 
Published: October 2022

Abstract

Background
Limited evidence exists regarding the impact of atrial fibrillation (AF) on outcomes after percutaneous mitral valve repair (PMVR). The aim of the present study was to compare 1-year clinical outcomes following PMVR in patients with and without AF.

Methods
426 patients with PMVR for severe MR were included in the COburg MItraclip (COMI) registry between 2016 and 2021. Patients were divided into an AF group (group A, n=284) and a non-AF group (group B, n=142). Clinical profiles, PMVR procedure characteristics and the clinical follow-up were compared between the two groups.

Results
Patients with AF were older (79.3±6.3 [AF] vs. 77.8±8 years [non-AF], p=0.03), had higher N-terminal B-type natriuretic peptide levels (NT-pro BNP: 5675±5544.2 vs 8516±11184.5, p=0.004), more often a coronary artery disease (62% vs 38%, p=0.03) and had a lower stroke risk (CHA2DS2-VASc score: 4.6±1.2 vs 4.9±1.3, p=0.01). There were no significant differences between groups with regard to the gender, logistic Euroscore or prevalence of chronic heart failure, hypertension, diabetes mellitus or severe mitral regurgitation. Acute procedural success (post-procedural 2. MR, 95.1% vs. 94.4%; p=0.76) and procedure-related major complications were similar.
There were no significant differences in 1-year MACCE (death, MI, stroke, bleeding), health-related quality of life or clinical improvement.

Conclusion
In patients with mitral regurgitation who underwent PMVR, AF is common and appears not to have a relevant negative impact on the clinical outcome at 1 year compared to patients with sinus rhythm.

Funding Acknowledgement
Type of funding sources: None.
Cryptogenic stroke and extrasystolic arrythmia: is there any correlation?
Authors: Germanova O , Germanov A V , Galati G 
Published: October 2022

Abstract

Up to 45% of all ischemic strokes (IS) are cryptogenic.

Purpose
To reveal the possible reasons of cryptogenic IS.

Methods
We analyzed the cases of computer tomography verified IS in patients admitted the hospital during the period of 3 years. All these 268 patients had unidentified source of IS. We analyzed hemostasiograms, lipids levels, performed echocardiography, Doppler ultrasound of brachiocephalic arteries, 24-hours ECG monitoring and common carotid arteries sphygmography (SG).

Results
None of the patients had atrial fibrillation, hemodynamically significant stenoses of brachiocephalic arteries or hematological pathology associated with hypercoagulation. 234 (87.3%) patients had atherosclerotic plaques in carotid area bifurcation (in 36 (13.4%) – intima-media thickness was 1.1 mm, in 74 (27.6%)– stenosis &lt;40%, in 124 (46.3%) had 40–69% stenosis in diameter). The internal carotid stenosis in diameter is calculated by ECST, NASCET and St. Mary's ratio criteria. To detect the type of the plaques we used Gray-Weale–Nicolaides ultrasound classification. In 39 (14.5%) was type I: uniformly echolucent plaque; in 88 (32.8%) type II: predominately echolucent plaque; in 71 (26.5%) type III: predominantly echogenic plaque, none had type IV: uniformly echogenic plaque or type V: heavy calcification. In 24-hours ECG monitoring and SG we revealed that most of the patients – 244 (91.0%) had extrasystolic arrhythmia which ventricular contraction of extrasystole appeared in the early phase of cardiocycle – before the transmitral blood flow peak. In 1st post-extrasystolic wave after such extrasystole we detected the growth of linear blood flow speed in carotid bifurcation (2.5 m/sec) and kinetic arteries parameters of SG (2.6 times).

Conclusion
The appearance of IS is higher in patients with extrasystolic arrhythmia appearing in the cardiocycle before the transmitral blood flow peak. In cryptogenic stroke, the reason of it can be the atherosclerotic plaque defragmentation with further embolism, caused by the additional mechanical trauma of increased hemodynamical and kinetic parameters of pulse wave of the 1st post-extrasystolic contraction.

Funding Acknowledgement
Type of funding sources: None.
Mobitz type I 2nd degree atrioventricular (Wenckebach) block and cardiovascular death using 978,901 12 lead ECGs recordings
Authors: Hendriksen S , Karlsen F M , Philbert B T , Person S , Koeber L , Torp-Pedersen C , Bang C N 
Published: October 2022

Abstract

Background
Mobitz type I 2nd degree atrioventricular (AV) block (Wenckebach) is usually considered benign. Guidelines recommend permanent cardiac pacing for patients with Mobitz type II second degree AV block (Mobitz II), but for patients with Wenckebach, permanent pacing is only indicated if the AV block causes symptoms or if the conductions delay occurs below the bundle of His. However, these guidelines are based on evidence of modest quality and a consensus amongst experts (1).

Purpose
This study aims to investigate if Wenckebach really is benign by comparing the risk of cardiovascular death for patients with Wenckebach to patients with normal ECGs.

Methods
This retrospective cohort study included 978,901 ECGs obtained from general practitioners in Denmark from 01/02/2001 to 31/10/2014. Index date was the day of the ECG recording and the patients were followed until death or end of follow up at December 2019.
The association between Wenckebach and cardiovascular death was analyzed using: 1) multivariate Cox models adjusted for age and comorbidities, 2) cause-specific Cox models and 3) cumulative risk and cause-specific hazard function plots, compared to matched controls. Information about comorbidities, pacemaker, indications, and death was retrieved from Danish nationwide registries.

Results
From the 978,901 ECG recordings, we found 262 patients with Wenckebach, 131 patients with Mobitz II, and 229,056 patients with normal ECGs. In Wenckebach, Mobitz II, and normal ECG the median age was 76, 80, and 50 years, 76%, 63%, and 41% were male, 25%, 16%, and 3% had diabetes, 35%, 30%, and 8% had hypertension, respectively.
During a mean follow-up of 11.2 years, cardiovascular death occurred in a total of 11,301 patients: 77 (29%) patients with Wenckebach, 40 (31%) patients with Mobitz II, and 11,184 (5%) patients with normal ECGs. In a matched cohort 262 Wenckebach patients were matched with 520 controls with normal ECGs. In the multivariate Cox model, Wenckebach was associated with cardiovascular death (HR: 2.14 [95% CI: 1.46–3.13], P&lt;0.001). Furthermore, in multivariate cause-specific Cox analysis with non-cardiovascular death and pacemaker as competing risk, Wenckebach was still associated with cardiovascular death (HR: 2.27 [95% CI: 1.37–3.75], P=0.001).
Furthermore, the results showed that 43% of the Wenckebach patients received pacemaker with a median time to pacemaker from ECG recording being 252 days. The vast majority of the Wenckebach patients who received pacemaker had a higher degree AV block than Wenckebach as indication for the implantation.

Conclusion
Wenckebach on routine ECG was associated with a significant higher hazard rate of cardiovascular death compared to matched controls with normal ECGs.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): The Danish Heart Association
Incidence of atrial and ventricular arrhythmias in patients with CIEDs and COVID-19
Authors: Margulescu A D , Thomas D E , Kakoudaki M , Cranch H , O'Dea J , Davies G , Phillips A , Green A S , Rees P , Barry J P 
Published: October 2022

Abstract

Background
It remains unclear whether COVID-19 infection is associated with increased arrhythmia burden in patients with cardiac implantable electronic devices (CIEDs).

Methods
We identified 46 patients tested positive for COVID-19 between 01/03/2020 and 31/05/2021 in our cohort of 1209 patients with CIED (3.8%). Data on arrhythmia burden during a 9 week period (a 4 week “pre-infection” period: P1, the week before the positive Covid-19 test: P2, and the 4 weeks afterwards: P3) was accessible in 35 patients.

Results
83% of patients were not hospitalised. Five patients (14.3%) (all non-hospitalised) had high rate atrial (HRA) events, 4 of which exclusively during P1 and/or P2. Thirty-two non-sustained VT (NSVT) episodes were recorded in 8 patients, one degenerating in VF requiring ICD shock (occurring in P2). One patient had frequent NSVT each week. After exclusion of this outlier, a numerical 4-fold increase in weekly NSVT episodes was observed between P1 and P3 (Patients with NSVT: 0.07±0.12 vs. 0.29±0.17 episodes/week, p=0.057; entire cohort: 0.015±0.060 vs. 0.059±0.138 episodes/week, p=0.16) (Figure 1). In P3, hospitalised patients had a trend towards higher NSVT burden vs. non-hospitalised patients (2/6 (33.3%) vs. 4/29 (13.8%), p=0.27) which was not apparent before the positive Covid-19 test.

Conclusion
Our single-centre experience suggests that COVID-19 infection may result in an increase in VA but not atrial arrhythmia burden in patients with CIED.

Funding Acknowledgement
Type of funding sources: None.