bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can echocardiography facilitate decision-making to CRT?
Authors: Puvrez A , Mirea O , Duchenne J , Beela A , Donal E , Voigt J U 
Published: October 2022

Abstract

Introduction
Cardiac resynchronization therapy (CRT) remains underused despite its well-established therapeutic effect and clear guidelines. Among various reasons are the lack of referral, the fear of complications and the high therapy cost. The assessment of mechanical dyssynchrony (MD) on echocardiography has been suggested to aid patient selection. In the past, however, several studies have used old markers of MD producing disappointing results and the use of echocardiography for patient selection became discredited. Promising new markers have been developed since and could aid clinical decision-making for CRT. These should, however, first be thoroughly tested and compared to the old markers.

Purpose
(I) To confirm the relevance of the new markers of MD for survival free of cardiac death and (II) to compare old and new markers of MD for predicting cardiac death within 5 years post-CRT in patients eligible for CRT according the 2021 ESC guidelines.

Methods
222 CRT-patients were analysed retrospectively in a multicentre setting. MD was assessed using three old markers: septal-to-posterior wall-motion-delay (SPWMD), left-ventricular-filling-time/cardiac-cycle ratio (LVFT/RR), and intraventricular mechanical delay (IVMD); and three new markers: systolic stretch index (SSI), myocardial work index (MWI), and visual presence of septal flash or apical rocking (SFoAR). For each marker, patients were categorized using previously published cut-offs as “MD present” (Yes) or “MD not present” (No). Log rank tests were performed on Kaplan-Meier curves for survival free of cardiac death. Cox proportional hazards regressions were used to compute the hazard-ratio (HR) for cardiac death within 5 years after implantation.

Results
Cardiac death occurred in 37 patients (17%). Patients with MD before CRT according to IVMD (p=0.003), SSI (p&lt;0.001), MWI (p&lt;0.001) or SFoAR (p&lt;0.001) had a significantly better survival. The hazard ratios were 0.34 (95% CI, 0.19–0.75) for IVMD, 0.30 (95% CI, 0.15–0.57) for SSI, 0.26 (95% CI, 0.12–0.54) for MWI and, 0.28 (95% CI, 0.14–0.53) for SFoAR. The other markers for MD were not significant for survival.

Conclusion
The new markers for dyssynchrony are better than the old. Patients with mechanical dyssynchrony on echocardiography before CRT according to SSI, MWI or SFoAR are 3 to 4 times less likely to die within 5 years after CRT implantation. The presence of one of these markers in patients with a broad QRS (≥130ms) and reduced LVEF (≤35%) should prompt clinicians to refer for or to proceed to CRT.

Funding Acknowledgement
Type of funding sources: None.
Pericoronary adipose tissue attenuation index (FAI) and its cardiovascular diagnostic and prognostic utility: a systematic review and meta-analysis
Authors: Sagris M , Antonopoulos A S A , Simantiris S S , Oikonomou E O , Siasos G S , Tsioufis K T , Tousoulis D T 
Published: October 2022

Abstract

Background
Pericoronary fat attenuation index (FAI) on coronary computed tomography angiography (CCTA) imaging has been proposed as a novel marker of coronary vascular inflammation with prognostic value for major cardiovascular events. To date though there is no systematic review of the published literature and no meta-analyzed data of previously published results.

Methods
We performed a systematic review and meta-analysis according to the PRISMA guidelines. We systematically explored published literature in MEDLINE (PubMed) before January 20, 2022 for studies assessing FAI in both diagnostic and prognostic clinical settings in patients with or without cardiovascular disease. The primary outcome was the mean difference in FAI attenuation between stable and unstable coronary plaques. The secondary outcome was the hazard ratio of high FAI values for future cardiovascular events. We calculated I2 to test heterogeneity. We used random-effects modelling for the meta-analyses to assess the primary and secondary outcomes. This study is registered with PROSPERO (CRD42021229491).

Results
In total, 20 studies referred in a total of 7,797 patients were included in this systematic review while 9 studies were used for the meta-analysis. FAI was significantly higher in unstable compared to stable plaques with a mean difference of 4.50 HU (95% CI: 1.10–7.89, I2=88%) among 902 patients. Higher pericoronary FAI values offered incremental prognostic value for major adverse cardiovascular events in studies with prospective follow-up (HR=3.29, 95% CI: 1.88–5.76, I2=75%) among 6,335 patients.

Conclusion
FAI is a promising imaging biomarker that may be successfully be used for detection of coronary inflammation, discrimination between stable and unstable plaques, and prognosis of future major adverse cardiovascular events. There is an undeniable need for further studies to establish the utility of this biomarker in clinical practice to improve coronary plaque discrimination and cardiovascular risk prognostication.

Funding Acknowledgement
Type of funding sources: None.
Effect of an optimized X-ray blanket design on operator radiation dose in cardiac catheterization based on real-world angiography
Authors: Davidsen C , Bolstad K , Ytre-Hauge K , Samnoey A , Vikenes K , Tuseth V 
Published: October 2022

Abstract

Background
There is increasing concern and focus in the interventional cardiology community on potential long term health issues related to radiation exposure and heavy wearable protection. Optimized shielding measures may reduce operator dose to levels where lighter radioprotective garments can safely be used, or even omitted. X-ray blankets (XRB) are commercially available but suffer from small size and lack of stability.

Purpose
The aim of this study is to assess shielding effect of an optimized XRB during cardiac catheterization and estimate the potential reduction in annual operator dose based on DICOM Radiation Dose Structured Report (RDSR) data reflecting everyday clinical practice.

Methods
Data accumulated from 7681 procedures over three years in our RDSR repository was used to identify projection angles and radiation doses during cardiac catheterization. Using an anthropomorphic phantom and a scatter radiation detector, radiation dose to the operator (mSv) and patient (dose area product – DAP) was measured for each angiographic projection for three different shielding setups. Relative operator dose (mSv/DAP) was calculated and multiplied by DAP per projection to estimate effect on operator dose.

Results
Adding an optimized XRB to a standard shielding setup comprising a table- and ceiling-mounted shield resulted in a 94.9% reduction in estimated operator dose. The largest shielding effect was observed in left and cranial projections where the ceiling-mounted shield offered less protection.

Conclusions
An optimized XRB is a simple shielding measure that has the potential to reduce operator dose.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Grieg Foundation
Relationship between OCT-derived plaque characteristics, CTA-derived coronary inflammation, and CMR-derived global coronary flow reserve in patients with acute coronary syndrome
Authors: Sugiyama T , Kanaji Y , Hoshino M , Hada M , Misawa T , Nagamine T , Ueno H , Matsuda K , Sayama K , Yonetsu T , Sasano T , Kakuta T 
Published: October 2022

Abstract

Background
The presence of layered plaque is suggestive of recurrent thrombotic events. However, the impact of layered plaque detected by optical coherence tomography (OCT) on coronary inflammation and coronary flow reserve remains unclear.

Purpose
We aimed to investigate the association of OCT-derived layered plaque with pericoronary adipose tissue inflammation assessed by coronary computed tomography angiography (cCTA) and global coronary flow reserve (G-CFR) assessed by cardiac magnetic resonance imaging (CMR) in patients with acute coronary syndrome (ACS).

Methods
We investigated 88 patients with first ACS who underwent preprocedural cCTA and OCT imaging of the culprit lesion, and CMR after percutaneous coronary intervention (PCI). All patients were divided into four groups according to the OCT-derived culprit plaque characteristics: layered vs. non-layered plaque; and plaque rupture vs. plaque erosion. Coronary inflammation was assessed by the mean value of pericoronary adipose tissue (PCAT) attenuation (−190 to −30 HU) of the three major coronary vessels. G-CFR was obtained by quantifying absolute coronary sinus flow at rest and during maximum hyperemia. CCTA and CMR findings were compared between the groups.

Results
In a total of 88 patients, layered plaque [L] with plaque rupture [PR] was observed in 25 patients, layered plaque with plaque erosion [PE] was observed in 26 patients, non-layered plaque [NL] with PR was observed in 23 patients, and non-layered plaque with PE was observed in 14 patients, respectively. Three-vessel-PCAT attenuation value (L-PR vs. L-PE vs. NL-PR vs. NL-PE; −68.13±6.18 vs. −69.01±6.72 vs. −69.76±4.04 vs. −74.61±5.63 HU, P=0.009) and culprit vessel PCAT attenuation value (L-PR vs. L-PE vs. NL-PR vs. NL-PE; −66.39±7.38 vs. −68.94±8.06 vs. −70.01±5.76 vs. −75.45±6.60 HU, P=0.003) showed the graded difference between the four groups. G-CFR value also showed the graded difference between the four groups (L-PR vs. L-PE vs. NL-PR vs. NL-PE; 2.26 [1.80–2.87] vs. 2.24 [1.72–3.13] vs. 2.97 [2.24–3.83] vs. 3.18 [2.67–4.08], P=0.022).

Conclusions
The presence of layered plaque at the culprit lesion was associated with high PCATA and low G-CFR in patients with ACS. Detection of layered plaque may indicate increased pericoronary inflammation and impaired coronary flow reserve, potentially providing the risk stratification in patients with ACS.

Funding Acknowledgement
Type of funding sources: None.
A novel clinical and cardiac magnetic resonance risk score for early risk prediction after ST-segment elevation myocardial infarction
Authors: Marcos Garces V , Perez N , Gavara J , Lopez-Lereu M P , Monmeneu J V , Rios-Navarro C , De Dios E , Merenciano-Gonzalez H , Gabaldon-Perez A , Chorro F J , Valente F , Lorenzatti D , Ortiz-Perez J T , Rodriguez-Palomares J F , Bodi V 
Published: October 2022

Abstract

Background
Cardiac magnetic resonance (CMR) performed early after ST-segment elevation myocardial infarction (STEMI) can improve major adverse cardiac event (MACE) risk prediction. However, predictive models including clinical and CMR variables are scarce and not routinely implemented in clinical practice.

Purpose
We aimed to create a simple clinical-CMR risk score for early MACE risk stratification in STEMI patients.

Methods
We performed a multicenter prospective registry in three Spanish university hospitals of reperfused STEMI patients (n=1118) in whom early (1-week) CMR-derived left ventricular ejection fraction (LVEF), infarct size and microvascular obstruction (MVO) were quantified. MACE was defined as a combined clinical endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (NF-MI) or re-admission for acute decompensated heart failure (HF), whichever occurred first. Univariate and multivariate analyses were performed and a risk score was computed using the variables which independently predicted the risk of MACE.

Results
During a median follow-up of 5.52 [2.63–7.44] years, 216 first MACE (58 CV deaths, 71 NF-MI and 87 HF) were registered. Mean age was 59.3±12.3 years and most patients (82.8%) were male. Based on the four variables independently associated with MACE, we computed an 8-point risk score: time to reperfusion &gt;4.15h (1 point), GRACE risk score &gt;155 (3 points), CMR-LVEF &lt;40% (3 points), and MVO &gt;1.5 segments (1 point). This score permitted MACE risk stratification: MACE per 100 person-years was 1.96 in the low-risk category (0–2 points), 5.44 in the intermediate-risk category (3–5 points), and 19.7 in the high-risk category (6–8 points): p&lt;0.001 in multivariable Cox survival analysis.

Conclusions
A novel risk score including clinical (time to reperfusion &gt;4.15h and GRACE risk score &gt;155) and CMR (LVEF &lt;40% and MVO &gt;1.5 segments) variables allows for simple and straightforward MACE risk stratification early after STEMI. External validation should confirm the applicability of the risk score.

Funding Acknowledgement
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) and Sociedad Española de Cardiología.
Pulmonary vein anatomical variants and incidence of atrial fibrillation
Authors: Gallen R , Apolinario M , Arsanjani R , Panse P , Jokerst C , Sorajja D 
Published: October 2022

Abstract

Introduction
Atrial fibrillation (AF) is the most common arrhythmia worldwide. The role of the pulmonary veins (PV) in its' pathogenesis has been well described, as have the most frequently seen anatomical variants of these veins. Prior studies have shown conflicting evidence on the potential association of PV variants and incidence of AF. We sought to reassess this association.

Methods
We conducted a retrospective case-control study of patients with AF (cases) and without AF (control group) undergoing cardiac CT imaging. We documented patient characteristics and cardiac anatomical features including PV variants, LV ejection fraction (EF) and left atrial (LA) volume/diameter.

Results
295 patients were included: 194 with AF and 101 without. 71% of AF cases were male. We showed a numerical difference for PV variants between the AF and control group that was not statistically significant (48.5% and 39.6%, p=0.15). The overall incidence of PV variants was higher than in previous studies. A significant association was identified between left atrial appendage (LAA) morphology and incidence of AF.

Conclusion
The suggested association between PV anatomical variants and the pathogenesis of AF may not be as clear-cut as previously thought. Our study is one of the largest of its kind and provides conflicting evidence with prior studies in this area. An improved understanding of the complex pathophysiology of AF and its relation to the pulmonary veins may help to guide future preventative and therapeutic strategies.

Funding Acknowledgement
Type of funding sources: None.
Effects of doxorubicin and ibrutinib on atrial arrhythmogenity: ex-vivo assessment in human myocardium
Authors: Berger Y , Primessnig U , Huettemeister J , Parwani A S , Boldt L H , Pieske B , Falk V , Grubitzsch H , Blaschke F , Heinzel F R 
Published: October 2022

Abstract

Introduction
The cytostatic drugs doxorubicin (Dox) and ibrutinib (Ibr) are established in the treatment of various tumor diseases. In (pre-) clinical studies, both chemotherapeutic agents showed cardiotoxic side effects, including atrial fibrillation [1]. In this context, patients with limited cardiac performance or diabetes might be particularly vulnerable, as these pre-existing conditions represent independent risk factors for cardiac complications [2].

Objectives
The dose-dependency of acute pro-arrhythmogenic effects of Dox and Ibr on the contractile activity of human atrial muscle tissue was investigated.

Patients and methods
Atrial samples were taken intraoperatively during cardiac procedures. Functional muscle strips were prepared from the cardiac trabeculae, followed by incubation with different concentrations of Dox or Ibr for 30 minutes. Subsequently, functional measurements were performed. Isometric contraction force and arrhythmogenic occurrences were recorded. The samples were consecutively exposed to external stressors during measurement (Fig. 1).
We evaluated the overall occurrence of arrhythmogenic contractions and during which phase of the protocol they occurred. The latter was expressed as degree of arrhythmogenesis (Fig. 1).
Following the functional measurements, the muscle strips were conserved at −80°C.

Results
We isolated 127 muscle strips from 29 patients. Highest rates of overall arrhythmic contractions were observed at 10μM Dox and 0.5μM Ibr (77.8 & 100% vs. 58.4% (control)). Mean degree of arrhythmogenesis increased from 1.63 (control) to 2.17 (10μM Dox) and 3.11 (0.5μM Ibr).
Analyzing our data according to the included individuals, treatment with Dox and Ibr enhanced the degree of arrhythmogenesis in the majority of patients. (Fig. 2)

Conclusion
Our protocol is suitable for investigating drug related acute pro-arrhythmogenic effects on human atrial myocardium. Treatment of isolated atrial myocardium with Dox and Ibr enhanced its susceptibility to arrhythmogenic occurrences. Optimal pro-arrhythmogenic conditions were observed at 10μM Dox and 0.5μM Ibr. The treated samples showed higher overall rates of arrhythmogenic contractions and the arrhythmogenic activity occurred earlier within our protocol.

Outlook
We will correlate the experimentally obtained data with clinical patient data, such as LVEF, BMI and diabetic status. The conserved muscle strips will be analyzed using standardized assays comparing post-translational modification (e.g. phosphorylation and oxidation) of key regulators of excitation contraction coupling (e.g. PKA, CaMKII, Ca2+ channels).

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): DZHK (German Centre for Cardiovascular Research), partner site Berlin
Dapagliflozin exhibits class I antiarrhythmic effects which suppress action potential formation in human atrial cardiomyocytes
Authors: Paasche A , Wiedmann F , Javorszky N , Yesilgoez B , Blochberger P , Kraft M , Frey N , Schmidt C 
Published: October 2022

Abstract

Background
Recently, inhibitors of sodium-glucose transporter 2 (SGLT2i) were shown to have tremendous cardioprotective effects in patients with type 2 diabetes mellitus (T2DM) as well as heart failure (HF) patients, regardless of their glycemic status. Among other beneficial effects on cardiovascular outcome an antiarrhythmic effect of SGLT2i was indicated. In patients with T2DM therapy with SGLT2i was associated with a significantly reduced risk of atrial arrhythmias and sudden cardiac death. As sodium-glucose transporter 2 (SGLT2) is not expressed within the heart underlying molecular modes of action remain unclear. Therefore, investigating possible antiarrhythmic mechanisms is crucial to determine whether SGLT2i might be beneficial for all patients suffering from arrhythmias, regardless of other comorbidities.

Purpose
To assess antiarrhythmic effects of SGLT2i on a molecular and cellular level. Therefore, direct electrophysiological effects of dapagliflozin – the most advanced SGLT2i in clinical trials – on action potential (AP) formation in atrial cardiomyocytes (CM) was investigated.

Methods
Effects of dapagliflozin on human NaV1.5, heterologously expressed in Chinese hamster ovary (CHO) cells, was investigated using the patch-clamp method. Further, effects on voltage-gated sodium channels (NaV) were also measured in human atrial CM. Consequences of dapagliflozin treatment on AP formation were studied on isolated human and porcine atrial CM using the patch-clamp technique. APs were elicited in current-clamp mode by injection of brief current pulses.

Results
Dapagliflozin (100 μM) significantly decreased peak sodium currents in human atrial CM as well as CHO cells, expressing human NaV1.5 channel subunits. Additionally, half-activation potential of voltage-gated sodium channels was significantly increased after administration of dapagliflozin. Furthermore, dapagliflozin (100 μM) suppressed AP formation in CM isolated from human and porcine left and right atrial tissue. In human CM action potential amplitude (APA) was significantly reduced by 34.3%, while APA inhibition by dapagliflozin averaged out at 30.7% for porcine CM. In porcine CM action potential duration at 50% (APD50) and 90% repolarization (APD90) were also significantly reduced.

Conclusion
Dapagliflozin suppresses AP formation in human and porcine atrial CM by inhibiting voltage-gated sodium currents. Therefore, we suppose that dapagliflozin exhibits class I antiarrhythmic effects.

Funding Acknowledgement
Type of funding sources: None.
“Concealed cardiomyopathy” is an important cause of autopsy-inconclusive sudden cardiac death and diagnosis impacts care of surviving relatives
Authors: Isbister J C , Nowak N , Yeates L , Singer E S , Sy R W , Ingles J , Raju H , Bagnall R , Semsarian C 
Published: October 2022

Abstract

Background
Genetic testing following sudden cardiac death (SCD) is currently guided by autopsy findings, despite the inherent challenges of autopsy examination and mounting evidence that malignant arrhythmia may occur prior to structural changes in inherited cardiomyopathy, so-called “concealed cardiomyopathy” (CCM).

Purpose
To identify the spectrum of genes implicated in autopsy-inconclusive SCD and describe the importance of identifying CCM for the ongoing care of SCD families.

Methods
Using a standardised framework for adjudication, autopsy-inconclusive SCD cases were identified as having a structurally normal heart or sub-diagnostic findings of uncertain significance on autopsy. Genetic variants were classified for pathogenicity using the American College of Medical Genetics and Genomics guidelines. Family follow-up was performed where possible.

Results
Twenty disease-causing variants were identified among 91 autopsy-inconclusive SCD cases (mean age 25.4±10.7 years) with a similar rate regardless of the presence or absence of sub-diagnostic findings (25.5% vs 18.2%, p=0.40). Cardiomyopathy-associated genes harboured 70% of clinically-actionable variants and were overrepresented in cases with sub-diagnostic structural changes at autopsy, accounting for 11 out of 12 disease-causing variants in this group (79% vs 21%, p=0.038, Figure 1, panel A). Variants in arrhythmogenic cardiomyopathy genes were the most common cause of CCM (9/14 CCM cases, Figure 1, panel B). Nearly two-thirds of genotype-positive relatives had an observable phenotype either on initial assessment or during subsequent follow-up. Twenty-seven genotype-negative first-degree relatives were released from ongoing screening.

Conclusion
The current paradigm of phenotype-directed genetic testing following SCD risks under recognition of CCM. Comprehensive evaluation of the decedent should include assessment of genes implicated in both cardiomyopathy and primary arrhythmias to improve diagnosis of CCM and optimise care for families.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart Foundation of Australia and National Health and Medical Research CouncilNew South Wales Health