bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of pocket infection during long- term follow- up
Authors: Vujadinovic N , Radovanovic NN , Milasinovic G , Pavlovic SU , Kircanski B , Brankovic N , Sajic V , Milasinovic A , Zivkovic M , Bisenic V
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

 Cardiac implantable electronic devices (CIEDs) are being implanted worldwide in increasing numbers, so the incidence of hospitalizations due to their infections is also increasing. 

Purpose

The aim of this study was to analyze the incidence of pocket infection related to the CIED procedure, as well as clinical presentation, diagnostic approach and methods of treatment during long-term follow- up on large cohort of patients. Methods: This was a retrospective, observational, single-center study. We enrolled patients who underwent CIED procedure between January 2011 and December 2015. The CIED procedure included implantation and replacement of the device. Pocket infection is defined as an infection limited to the generator pocket and can be presented from redness, swelling, pain to the skin erosion with exposure of the generator and/or leads. It may also be associated with lead infections and systemic CIED infections and/or infective endocarditis. All patients with CIED infection underwent the same diagnostics: complete blood count and inflammatory markers, pocket swab, three sets of blood cultures and echocardiography. Results: During the observed period 5 969 CIED procedures were performed (anti-bradycardia pacemakers 68.6%; ICD 21.4%; CRT-P/D 10.0%; CIED replacement 26.1%). CIED infection was registered in 41 patients (0.68%), most often after the ICD procedure (59.0%). In 22 patients (53.6%) the infection occurred after primo-implantation. The average time from intervention to infection was 17 ± 7.3 months. The mean follow-up was 52.2 ± 13.4 months. The most common manifestations of infection were redness (68.1%) and swelling (56.0%), then the protrusion of the generator or electrode (41.5%). Pacemaker pocket swabs and wound swabs were positive in 61.1% of samples and coagulase negative staphylococcus was found to be the most prevalent cause of infection (64.2%). The hemoculture test was positive in 10 patients, and the isolated causative agent matched the swab finding. The valvular vegetation was found in 4 patients. Pacemaker removal and surgical wound treatment were performed in all patients. Complete removal of all leads was achieved in 32 patients. In all pacemaker dependent patients and patients with ICD implanted in the secondary prevention of sudden cardiac death, reimplantation of the new device was performed in the same hospitalization on the opposite side. The remaining patients were operated on 3 to 4 weeks after the end of treatment.  Conclusions: It has been shown that the risk of pocket infection was low in a large number of patients, during long-term follow-up. The risk was higher in patients with ICD devices, and slightly higher after primo-implantation.
The incidence and clinical ramifications for leadless pacemaker fixation mechanism exposure on the epicardial surface
Authors: Breeman KTN , Burke MC , Shuros A , Soltis B , Brisben A , Kilvington J , Swackhamer B , Knops RE , Tjong FVY
Published: May 2021

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Boston Scientific and Abbott

Background

Leadless pacemaker (LP) fixation mechanism exposure (FE) by penetration of the epicardial surface has been described. Previously reported animal model studies showed FE for 7/10 Micra LPs, versus 4/10 CapSureFix Novus RV pacing leads (both Medtronic). However, it is unknown whether FE causes pericardial effusion or pericarditis or does not have clinical significance.

Purpose

To determine the incidence of FE of a novel LP in a chronic animal model and its association with acute or chronic pericardial effusion.

Methods

 Canine subjects were implanted with novel LPs (Boston Scientific) in an ongoing study. Acute pericardial effusion was assessed by post-procedural transthoracic echocardiography (TTE). Chronic pericardial effusion was assessed by TTE 90 days after implantation and post-mortem assessed pericardial fluid colour (PFC) and volume (PFV). FE was assessed visually at necropsy. Mann-Whitney U tests and chi-squared tests were used to determine whether greater PFV, more haemorrhagic PFC or LP implantation location differed significantly between subjects with and without FE.

Results

 Results to date are reported. Canine subjects (n = 71) were chronically implanted with LPs. Due to 14 in-vivo retrievals, data is shown of 57 subjects with LPs in situ at necropsy. Pre-deployment radiocontrast injection confirmed LP position (RV apex n = 41; RV apicoseptal n = 16), and mechanical stability and electrical testing confirmed adequate talon fixation after deployment. Necropsy after median 94 days (IQR 91-540) demonstrated FE in 11 cases (19%) (figure). No acute nor chronic pericardial effusion was seen on TTE. Mean PFV for animals with and without FE was 1.8 and 1.6 cc, respectively. FE did not show an association with PFV or colour (p= 0.53 and p = 0.83, respectively). For two animals, PFV and PFC are not available; FE was not observed in either of these cases. LP implantation location was not associated with incidence of FE (p = 1.00).

Conclusion

 Fixation mechanism exposure by the talons of a novel leadless pacemaker was observed in 19% of animals implanted and was not associated with acute or chronic pericardial effusion. Abstract Figure 1
Tricuspid and mitral valve regurgitation in a chronic canine model implanted with a novel leadless pacemaker
Authors: Breeman KTN , Knops RE , Swackhamer B , Kilvington J , Soltis B , Shuros A , Brisben A , Carter N , Burke MC , Tjong FVY
Published: May 2021

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Boston Scientific and Abbott

Background

 One of the presumed advantages of leadless pacemaker (LP) therapy is that tricuspid regurgitation (TR) occurrence and severity would be less than with conventional pacemakers due to the absence of leads. However, TR and mitral regurgitation (MR) may also worsen due to chronic right ventricular (RV) pacing per se.

Purpose

 To determine whether a novel LP is associated with increased TR and MR severity in a chronic canine model and to evaluate predictors of TR and MR worsening.

Methods

 Healthy canine subjects were implanted with a novel LP programmed at a lower rate of 80/min. TR and MR were assessed by transthoracic echocardiography (TTE) prior to implant, at 90 days and at 18 months after implant. Further were assessed percentage of pacing, presence of pacing during TTE, and wall motion abnormalities (WMA) observed during TTE, indicating ventriculo-ventricular dyssynchronous pacing. Paired t-tests were performed to compare TR and MR severity before and after implant. Univariable and multivariable generalized estimating equation (GEE) models were used to evaluate factors predictive of increased TR and MR severity. Paired t-tests were used to evaluate whether the increase of TR and MR differed between subgroups where pacing or WMA were observed or not.

Results

 An LP was implanted in 73 subjects. TR and MR severity at 90 days (n = 55) were significantly increased from baseline (p = 0.02 and 0.001, confidence intervals [CIs] 0.05-0.64 and 0.20-0.75, respectively); at 18 months (n = 37) TR severity remained significantly increased but MR did not (p = 0.01 and 0.62, CI [0.09, 0.69] and [-0.15, 0.25], respectively). Multivariable GEE (figure) showed that WMA and absence of TR at baseline are significant predictors for increased TR, while WMA and a shorter RV long axis are significant predictors for increased MR. Subgroup analysis demonstrated that TR and MR at day 90 were only significantly increased in subjects with observed pacing or WMA (n = 29; p = 0.0014 and p < 0.0001 respectively), but not in subjects without observed pacing or WMA (n = 26; p = 0.56 and 0.16, respectively). At 18 months, the same observation was found for TR but not MR (pacing or WMA [n = 15], p < 0.0001 and p = 0.33 respectively: no pacing or WMA [n = 26], p = 0.23 and 1, respectively).

Conclusion

 In absence of pacing, the novel EMPOWER LP was not associated with increased TR and MR severity in a canine model. When pacing was observed TR and MR did increase. Increased MR severity did not persist at 18 months. Abstract Figure 1
PROMET: The effect of operator profession on non-laser transvenous lead extraction
Authors: Akhtar Z , Gallagher MM , Elbatran A , Starck CT , Leung L WM , Sohal M
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

OnBehalf

PROMET group

Background

As implantation of cardiac implantable devices (CIED) rises globally, there is a paralleled need for extraction of these devices. Indications for transvenous lead extraction (TLE) is expanding, fuelling demand. This lifesaving procedure is performed by cardiologists and cardiac surgeons (CS). Cardiologists are familiar with transvenous methods whilst cardiac surgeons possess the skillset to address the significant complications associated with this procedure.

We compared non-laser TLE outcomes performed by cardiologists and cardiac surgeons from six high-volume extraction centres across Europe.

Methods

Data was collected retrospectively from six major European TLE centres of 2205 patients and 3849 leads (PROMET). Propensity 1:1 score matching (PSM) was performed to account for confounding variables. PSM model with variables: lead dwell time, infection indication, biventricular system and defibrillator device, was best matched. This dataset was analysed to compare outcomes of TLE performed by the cardiologists and CS. Predictors of 30-day mortality and complications were identified using a multivariate regression analysis.

Results

Patients treated by CS and cardiologists were similar in age (64.7 vs 66.7 years, p = NS) and equally male (70.3% vs 72.3%, p = 0.39) with a parallel infectious indication (51.7% vs 47.6%, p = 0.1). Surgeons achieved a significantly higher proportion of clinical success than cardiologists (98.9% vs 96.4%, p = 0.001) and complete lead extraction (98% vs 95.9%, p < 0.01) with a higher rate of minor complications (4.1% vs 2.2%, p = 0.024); major complications were similar (0.9% vs 1.2%, respectively, p = 0.46) as was 30-day mortality (3.2% vs 2%, respectively, p = 0.28). Multivariate regression analysis revealed systemic infection (p < 0.001, OR 7.2 [CI 2.3-20.1]) and defibrillator system extraction (p = 0.025, OR 3.4 [CI 1.2-10.2]) increased the odds of 30-day mortality, whilst Evolution™ sheath use reduced the odds (p = 0.025, OR 0.34 [CI 0.13-0.88]); lead dwell time (p = 0.02, OR 1.005 [1-1.009] and Evolution™ sheath use (p = 0.023, OR 2.15[1.1-4.15]) increased the odds of complications.

Conclusion

Cardiac surgeons and cardiologists achieved a high rate of TLE procedural success and with a similar safety profile, replicating standards seen across Europe.
Impact of pulmonary valve replacement on ventricular arrhythmias in patients with tetralogy of Fallot
Authors: Bessiere F , Gardey K , Duthoit G , Koutbi L , Labombarda F , Marquie C , Gourraud JB , Mondoly P , Bordachar P , Martins R , Pasquie JL , Combes N , Di Filippo S , Marijon E , Waldmann V
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): INSERM - French Society of Cardiology

OnBehalf

DAIT4F Investigators

Background

Sudden cardiac death is a major cause of death in tetralogy of Fallot (TOF) and right ventricular overload is commonly considered as a potential trigger for ventricular arrhythmias.

Purpose

We aimed to assess the impact of pulmonary valve replacement (PVR) on ventricular arrhythmias burden using a population of TOF patients with continuous cardiac monitoring by implantable cardioverter defibrillator (ICD).

Methods

Nationwide French registry including all TOF patients with an ICD. Survival data with recurrent events were used to compare the burden of appropriate ICD therapies before and after PVR in patients who underwent PVR over the study period.

Results

A total of 165 patients (mean age 42.2 ± 13.3 years, 70.1% males) were included from 40 centers. Over a median (IQR) follow-up period of 6.8 (2.5-11.4) years, 26 (15.8%) patients underwent PVR. Among those patients, 18 (69.2%) experienced at least one appropriate ICD therapy. When considering all ICD therapies delivered before (n = 62) and after (n = 16) PVR, the burden of ICD appropriate therapies was significantly lower after PVR (HR 0.21, 95%CI 0.08-0.56, p = 0.002). In the overall cohort, PVR before ICD implantation was also independently associated with a lower risk of appropriate ICD therapy in primary prevention patients (HR 0.29, 95%CI 0.10-0.89, p = 0.031).

Conclusions

In this cohort of high-risk TOF patients implanted with an ICD, the burden of appropriate ICD therapies was significantly reduced after PVR. While optimal indications and timing for PVR are debated, these findings suggest the importance of considering ventricular arrhythmias in the overall making-decision process. Abstract Figure.
Implantable cardioverter defibrillators in adult congenital heart disease: long-term follow up of therapies, complications and clinical events
Authors: Ferreira V , Cruz Coutinho M , Portugal G , Silva Cunha P , Valente B , Laranjo S , Branco Mano T , Castelo A , Garcia Bras P , Cardoso I , Bras M , Sousa L , Oliveira M
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Adults with congenital heart disease (ACHD) at increased risk for sudden cardiac death (SCD) often undergo implantable cardioverter defibrillator (ICD) implantation at young ages. Data evaluating the long-term outcomes of ICD in this population remain scarce. We aimed to characterize the population with ACHD and an ICD.

Methods

Consecutive ACHD submitted to an ICD implantation in a single tertiary center were evaluated. Data on baseline clinical features, heart defect, indication for ICD, type of device, ICD-related complication and therapies and mortality during follow-up were collected.

Results

A total of 34 patients (P) were evaluated. Median age at implant was 39.3 years (interquartile range [IQR] 29-5-53.6) and median left ventricular ejection fraction (LVEF) was 43.5% (IQR 28.0-53.3). The most common heart defect was tetralogy of Fallot (11P;32,3%), followed by dextro-transposition of the great arteries, ostium secundum atrial septal defect (ASD) and ventricular septal defect (Figure 1). All P were submitted to surgical correction (median age at surgery 12.5 years [IQR 3.0-29.1]). Sixteen P underwent ICD implantation for primary prevention of SCD, owing to complex cardiopathy and ventricular dysfunction, and 18P due to spontaneous ventricular tachyarrhythmias. The implantable devices were a single-chamber ICD in 55.9%, a double-chamber ICD in 17.6%, a subcutaneous ICD in 20.6% and a CRT-D in 5.9%. During a median follow-up of 4.5 years (IQR 2.1-8.8), 52.9% of the P received appropriate ICD therapies, corresponding to 37.5% and 66.7% of primary and secondary prevention P, respectively. Median time to first arrhythmic event was 25.3 months (IQR 13.7-52.9). Six P (17.6%) suffered ICD-related complications and 20.6% received inappropriate therapies due to supraventricular tachyarrhythmias. During follow-up, 8.8% were submitted to heart transplant and 29.4% died (Table 1).  ICD therapies were associated with a composite of death, cardiac transplantation and hospital admission (OR 5.0, 95% CI 1.0-24.3).

Conclusion

ACHD with ICD experience high rate of appropriate therapies, including those implanted for primary prevention. The long-term burden of ICD-related complications and inappropriate shocks underlines the need for careful risk stratification and close monitoring. The increased survival of this population justifies collecting data on long-term outcomes to improve its care. Abstract Figure.
A novel diagnostic score to differentiate between athlete"s heart and ARVC
Authors: Rossi VA , Niederseer D , Sokolska JM , Kovacs B , Costa S , Gasperetti A , Brunckhorst CB , Akdis D , Tanner FC , Duru F , Schmied CM , Saguner AM
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

The 2010 Task Force Criteria (TFC), although representing the current gold standard to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC), have not been tested to differentiate ARVC from the athlete’s heart. Furthermore, not all 6 diagnostic categories are easy to obtain.

Purpose

We hypothesized that atrial dimensions are useful to differentiate between both entities. Therefore, we developed a new diagnostic score based upon readily available clinical parameters including atrial dimensions on TTE to help distinguishing the athlete’s heart from ARVC in daily clinical practice.

Methods

In this observational study, 37 patients with definite ARVC (from the Zurich ARVC Program) were compared to 68 athletes. Base on ROC analysis, the following echocardiographic, laboratory and electrocardiographic parameters were included in the final score: indexed right/left atrial volumes (RAVI/LAVI ratio), NT-proBNP, RVOT measurements (PLAX and PSAX adjusted for BSA) on TTE, tricuspid annular motion velocity (TAM) on TTE, precordial electrocardiographic T-wave inversions and depolarization abnormalities according to the TFC.

Results

ARVC patients had a higher RAVI/LAVI ratio (1.78 ± 1.6vs0.95 ± 0.3,p < 0.001), lower right-ventricular function (fac:28 ± 9.7vs42.1 ± 4.8%,p < 0.001; TAM:17.9 ± 5.6vs23.3 ± 3.7mm,p < 0.001) and higher serum NT-proBNP levels (491 ± 771vs44.8 ± 50.6ng/l,p < 0.001). Our novel score outperformed the performance of the 2010 TFC using those parameters, which are available in routine clinical practice (AUC95%,p < 0.001(95%CI.91-.99)vs.AUC90%,p < 0.001(95%CI.84-.97). A score value of 7/12 points yielded a specificity of 98% and a sensitivity of 61% for a diagnosis of ARVC.

Conclusions

ARVC patients present with significantly larger RA as compared to athletes, resulting in a greater RAVI/LAVI ratio. Our novel diagnostic score includes readily available clinical parameters and has a high diagnostic accuracy to differentiate between ARVC and the athlete´s heart. Abstract Figure. Novel clinical score
Remote app-based management of atrial fibrillation during the COVID-19: The centre characteristics and experiences of the European TeleCheck-AF project
Authors: Linz D , Pluymaekers N , Hermans A , Van Der Velden R , Verhaert D , Gupta D , Steven D , Duncker D , Manninger M , Svennberg E , Heidbuchel H , Crijns H , Sahaib A , Tomlinson D , Hendriks J
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

OnBehalf

TeleCheck-AF Investigators

Aims

Herein we describe the characteristics, inclusion rates and experiences from participating centres in the European TeleCheck-AF project. TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck®). 

Methods

Two surveys exploring centre characteristics (n = 25) and centre experiences (n = 23) were completed.

Results

Most centres were academic (64%) and specialized public cardiology/district hospitals (36%). Majority of centres had AF outpatient clinics (64%) and only 36% had AF ablation clinics. The time required to start patient inclusion and total number of included patients in the project was comparable for centres experienced (56%) or inexperienced in mHealth use. Within 28 weeks, 1930 AF patients were recruited, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). Average inclusion rate was highest during the lockdown restrictions and reached a steady state at a lower level after easing the restrictions (188 vs 52 weekly recruited patients). Majority (>80%) of the centres reported no problems during the implementation of the TeleCheck-AF approach. Centres agreed that the on-boarding process of their center in the TeleCheck-AF project was simple and access to the patients measurements via stand-alone cloud infrastructure was trouble-free and possible from the first day on. They also agreed that remote heart rate and rhythm assessment by the FibriCheck® app around teleconsulatation supported their medical decision making; that their patients responded positively to use FibriCheck® for seven days; and that they felt comfortable to interpret PPG recordings. 

Conclusions

Despite different health care settings and mHealth experiences, the TeleCheck-AF approach could be set up within an extremely short time and easily used in different European centres during COVID-19. Abstract Figure.
What can we find in the ECG recording in convalescent from COVID-19 with mild and moderate course
Authors: Chudzik M , Oszczygiel E , Miskowiec D , Kasprzak JD
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Despite the fact that most people with COVID-19 (C-19) do not require hospitalization, little is known about the changes in ECG in this group of patients (pts). The electrocardiogram (ECG) is one of the leading tools to assess the extent of cardiac involvement in C-19 pts.

Our main aim was to asses ECG abnormalities related to cardiac involvement in patients without hospitalization with mild and moderate course of C-19 .

Methods

Only pts without  co morbidities, not taking any medications were included to the study.  In all pts  standard 12-lead electrocardiograms (EKG)  mean 8,2week +/- 4,6) after C-19 was  performed in supine position after 15 minutes in rest.  The following parameters were analyzed: mean heart rate (mHR), bradycardia and tachycardia episodes defined as HR <40bpm and  HR> 100 bpm, PQ duration, QRS durations,  the Bazett-corrected QT interval, changes in the ST-T segment and the T wave. Additionally heart rhythm disturbances were assessed and atrial fibrillation/flutter episodes, the presence of atrial premature contractions (APCs), ventricular premature contractions VES) Number of atrioventricular blocks, bundle branch blocs (BBB) – (RBBB, LBBB, a nonspecific intraventricular conduction block) were also analyzed.

Results

264 pts were included to final assessment, with mean age 43,5 ± 13,5 years. The results were as follow: HR <40bpm - in 0pts, HR> 100 bpm in 9(3%)pts, PQ duration > 200ms in 7(3%)pts, QRS durations > 100ms in 19(6%)pts, QTc interval in 16 (6%)pts, ST-T segment abnormalities in 21(8%)pts and the T wave abnormalities in16(6%)pts Following heart rhythm disturbances were noted: AF/AFl in 0pts, (APCs) in 0pts, VES – in 3(1%)pts. No episodes of atrioventricular blocks were recorded, but BB in bundle branch blocs (BBB) – (RBBB, LBBB, a nonspecific intraventricular conduction block)  in 14 (3%) pts were noted.

Conclusions. The most frequent ECG abnormalities in pts without co-morbidities after COVID-19 without hospitalization were ST-T segment and T abnormalities. A large number of changes in ECG confirms that we can expect cardiac involvement also in the group of patients with mild and moderate course of COVID-19.
Novel oral anticoagulats for the treatment of left ventricle thrombosis: a systematic review and meta-analysis
Authors: Serenelli M , Vitali F , Pavasini R , Tonet E , Pompei G , Passarini G , Tolomeo P , Enriquez A , Guardigli G , Campo G , Bertini M
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

novel oral anticoagulants (NOACs) are not guideline-recommanded treatment for left ventricular thrombus.  Purpose: the aim of this meta-analysis is to compare NOACs versus vitamin-K atagonsits (VKAs) efficacy in treating left ventricular thrombus (LVT). Methods: we systematically searched MEDLINE, Cochrane Library, Biomed Central, and Web of Science for trials comparing NOACs versus VKAs in the setting of LVT. Five studies, out of the 74 initially selected after first screening, were included in the meta-analysis. For the development of this meta-analysis, the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. The shortlisted studies were retrieved as full articles and appraised independently by two unblinded reviewers. The Mantel-Haensel method with a random effect model was used for the pooled analysis. The primary outcome was the occurrence of stroke and systemic embolism. Secondary outcome was occurrence of left ventricular thrombosis resolution during treatment.  Results: 707 patients were included in the analysis for the primary outcome. Of these, 230 were treated with NOACs and 477 with VKAs. The pooled OR for the primary outcome was 0.71 (95% CI 0.18-2.86, I2 67%), thus showing similar effect in term of ischaemic protection. A total of 698 patients, 228 on NOACs and 470 on VKAs were included in the analysis of the secondary outcome. The pooled OR for the secondary outcome pooled OR 0.97, 95% CI 0.56-1.68, I2 46%. Conclusions and Relevance: NOACs seem to have a similar efficacy profile compare to VKAs and so they should be considered as an alternative treatment for left ventricular thrombosis. Large prospective randomized clinical trials are needed to confirm this exploratory finding. Abstract Figure 1
SERCA2a stimulation by istaroxime improves intracellular Ca2+ handling and diastolic dysfunction in a model of diabetic cardiomyopathy
Authors: Torre E , Arici M , Lodrini AM , Ferrandi M , Barassi P , Hsu SC , Chang GJ , Altomare C , Ferrari P , Bianchi G , Rocchetti M
Published: May 2021

Funding Acknowledgements

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by CVie Therapeutics Limited (Taipei, Taiwan) and Windtree Therapeutics (Warrington, USA)

Diabetic cardiomyopathy is a multifactorial disease characterized by an early onset of diastolic dysfunction (DD) that precedes the development of systolic impairment. Mechanisms that can restore cardiac relaxation improving intracellular Ca2+ dynamics represent a promising therapeutic approach for cardiovascular diseases associated to DD. Istaroxime has the double property to accelerate Ca2+ uptake into sarcoplasmic reticulum (SR) through the SR Ca2+ pump (SERCA2a) stimulation and to inhibit Na+/K+ ATPase (NKA). The project aims to characterize istaroxime effects at a concentration (100 nM) marginally affecting NKA, in order to highlight its effects dependent on the stimulation of SERCA2a in a model of mild diabetes.

Streptozotocin (STZ) treated diabetic rats were studied at 9 weeks after STZ injection in comparison to controls (CTR). Istaroxime effects were evaluated in vivo and in left ventricular (LV) preparations. STZ animals showed 1) marked DD not associated to cardiac fibrosis, 2) LV mass reduction associated to reduced LV cell dimension and T-tubules loss, 3) reduced LV SERCA2 protein level and activity and 4) slower SR Ca2+ uptake rate, 5) LV action potential (AP) prolongation and increased short-term variability (STV) of AP duration, 6) increased diastolic Ca2+, 7) unaltered SR Ca2+ content and stability in intact cells. Acute istaroxime infusion (0.11 mg/kg/min for 15 min) reduced DD in STZ rats. Accordingly, in STZ myocytes istaroxime (100 nM) stimulated SERCA2a activity and blunted STZ-induced abnormalities in LV Ca2+ dynamics. In CTR myocytes, istaroxime increased diastolic Ca2+ level due to NKA blockade albeit minimal, while its effects on SERCA2a were almost absent.

SERCA2a stimulation by istaroxime improved STZ-induced DD and intracellular Ca2+ handling anomalies. Thus, SERCA2a stimulation can be considered a promising therapeutic approach for DD treatment. Abstract Figure.
Effect of adipose graft transposition procedure (AGTP) on the ischemic arrhythmogenic substrate: an MRI study in a swine model of chronic myocardial infraction
Authors: Adelino Recasens R , Galvez-Monton C , Teis A , Martinez-Falguera D , Rodriguez-Leor O , Fadeuilhe E , Sarrias A , Villuendas R , Bazan V , Aranyo J , Prat C , Bayes-Genis A , Curiel C , Marsal R , Bisbal F
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III

BACKGROUND

Cardiac regenerative therapy is a promising treatment for patients with myocardial infarction (MI) and heart failure. Nevertheless, previous ex-vivo studies have raised concern on the potential increased risk of arrhythmic events following certain cell therapies. Adipose graft transposition procedure (AGTP) is a cardiac reparative therapy consisting in transposing a vascularized adipose flap from the autologous pericardium and placing it over the epicardial scar area and has demonstrated to reduce infarct size and improve the left ventricular ejection fraction in preclinical and human studies.

PURPOSE

To assess the effect of the AGTP on the post-MI scar composition and image-based ventricular tachycardia (VT) corridors detection by means of late gadolinium enhanced cardiac magnetic resonance (LGE-CMR).

METHODS

A left circumflex artery (first marginal branch) MI was induced in 9 Landrace X Large White Pigs by delivering 1-3 coils. Two weeks post-MI, all subjects underwent a 3 Tesla LGE-CMR and randomized to the AGTP or sham group. LGE-CMR was repeated 30 days post-treatment (6 weeks post-MI). The arrhythmogenic substrate was characterized with an advanced image post-processing tool (ADAS 3D) and included quantification of dense scar and border zone (BZ) mass and detection of ventricular tachycardia (VT) corridors (including corridor scar mass).

RESULTS

The overall scar mass did not differ between scans in the overall population (7.6 ± 3.5 g vs 7.5 ± 2.2 g in the baseline and post-treatment scans, respectively; p = 0.9). Compared to the sham subjects, those receiving AGTP showed an absolute reduction of the total (-3.2 ± 1.4 g vs. +2.4 ± 1.7 g, p = 0.04) and dense scar (-0.9 ± 0.4 g vs. +0.7 ± 0.5 g, p = 0.03). BZ mass tended to decrease in the AGTP group (-2.2 vs 1.63 g; p = 0.06). The AGTP group showed a trend to reduce the number of VT corridors (-1 ± 0.7 vs. +0.4 ± 0.2, p = 0.078) and corridor scar mass (-0.3 ± 0.26 g vs. +0.1 ± 0.1 g, p = 0.11) (figure).

CONCLUSIONS

Cardiac reparative therapy of MI with AGTP reduced dense scar mass, compared to the increase observed in the sham group. The trend to reduce the BZ mass and the number/mass of VT corridors suggests a beneficial effect on the arrhythmic remodeling of the post-MI scar. Abstract Figure. Reduction in corridor"s number
Clinical, genetic and functional analysis of R562S-Kv7.1 mutation associated with long QT syndrome type 1
Authors: Svecova O , Kula R , Chmelikova L , Hosek J , Synkova I , Novotny T , Bebarova M
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): Ministry of Education, Youth and Sports of the Czech Republic

Introduction

Loss-of-function variants of the KCNQ1 gene are associated with life-threatening arrhythmogenic long QT syndrome type 1 (LQT1). This gene encodes structure of the slow delayed rectifier potassium channel (IKs). Some functional characteristics of the C-terminal KCNQ1 variant c.1686G > C (p.R562S) have been recently described [1]. However, accumulation of the current under beta-adrenergic stimulation, essential for shortening the action potential duration during exercise, have not been tested.

Purpose

The aim of this study was to analyse clinical and genetic characteristics of the R562S variant in our patients and to investigate impact of the variant on IKs channel function with a special focus on reactivity of the channels on beta-adrenergic stimulation.

Methods

The clinical diagnosis was established according to ESC Guidelines including QTc analysis at rest and after exercise. The molecular genetics diagnostics followed according to current practices (the massive parallel sequencing since 2016). The biophysical analysis was performed on Chinese hamster ovary cells (CHO) by the whole cell patch clamp technique at 37 °C. CHO cells were transiently transfected with wild type (WT) and/or R562S human IKs channels (KCNQ1/KCNE1/Yotiao, 1:2:4). Cyclic adenosine monophosphate (cAMP, 200 µM) and okadaic acid (OA, 0.2 µM) in the pipette solution were used to simulate the beta-adrenergic stimulation. In the confocal microscopy experiments, expression of Yotiao was omitted and GFP-tagged KCNQ1 was used.

Results

The variant R562S-Kv7.1 has been identified in 7 heterozygous carriers from 3 putatively unrelated families in the Czech Republic. The genotype was associated with long QT syndrome phenotype (prolonged QTc, symptoms including syncopes and aborted cardiac arrest) in some of the carriers. The basic functional analysis proved that both homozygous and heterozygous R562S channels are expressed on the cell membrane (confocal microscopy) and carry IKs (whole cell patch clamp) which agrees with the recently published data on this variant. Importantly, reactivity on beta-adrenergic stimulation was absent in both homozygous and heterozygous R562S channels (n = 14 and 8, respectively), but present in the wild-type channels (increase by 51.4 ± 11.1 % at 120-s cAMP/OA diffusion; n = 12).

Conclusions

The R562S-Kv7.1 variant may be a founder LQT1 variant in our region which will be further investigated in the future. This variant impairs response of IKs channel to beta-adrenergic stimulation. Absence of this essential regulation may considerably aggravate the channel dysfunction and, thus, may result in life-threatening arrhythmias in R562S carriers during exercise.
Culture conditions effect properties of the Na+/K+-ATPase pump current in hiPSC cardiomyocytes
Authors: Ismaili D , Gurr K , Horvath A , Hansen A , Eschenhagen T , Christ T
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BMBF

Background

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) provide an opportunity to study human cardiac physiology and pathophysiology or to use for cardiac repair as well as for cardiovascular drug testing. Suitability for these purposes requires generating hiPSC cardiomyocytes that share typical electrophysiological properties of adult human cardiomyocytes. In the human heart the Na+/K+-ATPase pump current plays a major role in the regulation of contractile force and electrical stability. So far there are no data about Na+/K+-ATPase pump current function in hiPSC cardiomyocytes available.

Purpose

We compared the properties of Na+/K+-ATPase pump current in hiPSC cardiomyocytes from conventional monolayers (ML) culture to three-dimensional engineered heart tissue (EHT).

Methods

HiPSC cardiomyocytes differentiated from in-house control hiPSC cell line C25 were dissociated from ML and EHT culture. Na+/K+-ATPase pump current was recorded by whole-cell patch clamp technique at 37°C. The holding potential was -40 mV to inactivate sodium current. Current was measured in the absence of K+ and after adding 5.4 mM potassium chloride (KCL). Na+/K+-ATPase pump current was defined as the ouabain (10 µM) sensitive current. Voltage-dependency of Na+/K+-ATPase pump was determined using rectangular voltage pulses (increasing from -120 mV to +60 mV).

Results

Outwardly directed Na+/K+-ATPase pump could be recorded at -40 mV when KCL was added to the bath solution (5.4 mM). Currents were larger in EHT than in ML (0.8 ± 0.08 pA/pF n = 16 ML vs. 1.29 ± 0.13 pA/pF n = 28 EHT; p < 0.05). The K+-induced outward current was abolished by ouabain. The K+- and ouabain-sensitive current densities were similar in size (0.84 ± 0.11 pA/pF n = 16 ML vs. 1.12 ± 0.11 pA/pF n = 28 EHT for ouabain), indicating the measured K+-induced current was Na+/K+-ATPase pump current. Increasing extracellular K+-concentration in a stepwise manner (0,25 mM, 0,5 mM, 1 mM, 2 mM, 5,4 mM and 10 mM) showed a concentration-dependent relationship to Na+/K+-ATPase pump current with throughout higher current densities in EHT compared to ML (sensitivity to K+ not different). Na+/K+-ATPase pump current showed expected voltage-dependency with +0.23 ± 0.13 pA/pF at -120 mV and +0.89 ± 0.16 pA/pF at +60 mV (n= 18) in ML and with +0.71 ± 0.17 pA/pF at -120 mV and +1.2 ± 0.2 pA/pF at +60 mV (n= 24) in EHT.

Conclusion

HiPSC cardiomyocytes possess Na+/K+-ATPase pump current. Current density is in the range of human cardiomyocytes in EHT but substantially smaller in ML. 3D culturing may be needed to develop the physiological properties of Na+/K+-ATPase pump current.
Electro-mechanical and mechano-electrical interactions in healthy and drug-induced LQTS rabbit hearts
Authors: Lewetag R , Hornyik T , Jacobi S , Moss R , Pilia N , Menza M , Perez-Feliz S , Bode C , Seemann G , Odening KE
Published: May 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): German Research Foundation

Background

Electrical and mechanical heterogeneities and their interactions (electro-mechanical and mechano-electrical coupling; EMC / MEC) are essential for normal cardiac function. Alterations in these can result in increased arrhythmia formation.

Purpose

With this study, we aim to investigate EMC and MEC under physiological and pathological conditions to better understand their roles in arrhythmia development.

Methods

Multi-channel ECG and TPM-MRI were used to measure regional differences in EMC in healthy ("control") and IKr-blocker E-4031 induced acute LQTS ("E-4031") rabbit hearts in vivo. MEC was studied in both groups by acutely changing mechanical function (increased preload by 6 ml/kg BW bolus of NaCl).

Results

In acute LQTS hearts (E-4031 10µg/kg bolus + 1µg/(kg*min) iv), cardiac repolarization was markedly prolonged compared to healthy controls, (p < 0.0001; n = 13), with increased QT-dispersion (Max-Min), a marker for regional heterogeneity of repolarization (p < 0.01; n = 13).

Changing electrical function by E-4031 resulted in changes of mechanical features (EMC): in acute LQTS hearts, diastolic longitudinal velocity (Vz) was reduced in all basal (p = 0.003; n = 19) and 4/6 mid segments (p = 0.006; n = 19). Longitudinal diastolic TTP was prolonged significantly in 5/6 basal and 4/6 mid segments by E-4031. These alterations led to an increased apicobasal heterogeneity of longitudinal contraction duration (basal-apical Vz_dia_TTP [ms] 2.9 ± 10.6 vs. 21.1 ± 21.3; p = 0.01; n = 9).

Increased preload acutely prolonged QTc in both "control" and "E-4031" hearts (‘control’ 156.6 ± 11.6 to 198.3 ± 20.3; p < 0.0001 vs. ‘E-4031’ 193.9 ± 19.6 to 256.0 ± 37.5; p < 0.0001; n = 13) (MEC). This effect was more pronounced in "E-4031" acute LQTS hearts than in healthy hearts (Figure 1; delta QTc [ms] ‘control’ 41.6 ± 14.9 vs. ‘E4031’ 62.1 ± 32.1; p < 0.006, n = 13). QT-dispersion (Max-Min) was increased significantly upon mechanical change only in "E-4031" (‘E-4031’ 25.8 ± 5.5 to 32.7 ± 12.3; p < 0.03, n = 13).

Conclusion

E-4031-induced changes in electrical function resulted in marked alterations in mechanical features via EMC. Similarly, acute changes in mechanical function (increased preload) resulted in electrical changes via MEC. Importantly, QT-prolonging effects of acutely increased preload, as well as its effects on regional heterogeneity of repolarization, were more pronounced in E-4031-induced acute LQTS hearts, indicating that cardiac repolarization in LQTS may be more susceptible to acute MEC effects than in healthy hearts. Acute MEC effects may thus play an additional role in LQT-related arrhythmogenesis. Abstract Figure.
MFAP4 deletion attenuates the progression of angiotensin II-induced atrial fibrosis and atrial fibrillation
Authors: Wang Huibo , Liu Mingxin , Wang Xixing , Shuai Wei , Fu Hui
Published: May 2021

Aims 

Microfibrillar-associated protein 4 (MFAP4) is associated with atrial fibrillation (AF). Nevertheless, the specific role and underlying mechanism of MFAP4 in atrial fibrosis, the hallmark of AF, remain undefined. This study aims to elucidate the role of MFAP4 in the regulation of atrial fibrosis and to explore the underlying mechanism.

Methods and results 

This study used MFAP4 knockout (MFAP4-KO) mice and their wild-type (WT) littermates to investigate the effect of angiotensin II (Ang II) (2000 ng/kg/min for 3 weeks) on atrial fibrosis and susceptibility to AF in terms of morphology, histology, electrophysiology, and molecular biology. MFAP4 deletion in mice did not alter cardiac structure and function at baseline. After treatment with Ang II, the MFAP4-KO mice showed a decreased left atrial enlargement and fibrosis, slowed atrial conduction, and reduced susceptibility to AF compared with the WT mice. Regarding the mechanism, we found that MFAP4 deletion markedly inhibited activated focal adhesion kinase (FAK)-mediated PI3K-AKT signalling and MEK1/2-ERK1/2 signalling after Ang II treatment.

Conclusions 

Overall, our study showed that loss of MFAP4 attenuates Ang II-mediated left atrial fibrosis and dilation and decreases susceptibility to AF by decreasing the phosphorylation of FAK and inhibiting the activation of the PI3K-AKT and MEK1/2-ERK1/2 signalling pathways. These findings further indicate that targeting MFAP4 may be a potential upstream therapeutic option for atrial fibrosis and AF.
Effect of seasonality on physico-chemical and microbiological properties of nicastrese milk and artisanal cheese
Authors: Pino Alessandra , Liotta Luigi , Caggia Cinzia , Chiofalo Vincenzo , De Nardo Floro , Zumbo Alessandro , Todaro Aldo , Randazzo Cinzia Lucia
Published: May 2021

Nicastrese is an indigenous Italian goat breed reared in the Calabria region under semi-extensive practices. From January to June, the milk yield of 400 multiparous Nicastrese goats was evaluated. In addition, tank milk and ripened cheese samples were subjected to physico-chemical and microbiological analyses with the aim to assess the effect of the seasonality on quality parameters. The volatile organic compounds profile of the ripened Nicastrese cheese samples was evaluated. Results showed that the seasonality had a significant effect on milk fat, lactose, urea, citric acid contents and acidity. Microbiological analysis of tank milk samples revealed variability among the different microbial groups investigated except for Escherichia coli. In addition, faecal coliforms and Listeria spp. were never detected. Regarding 60 days ripened cheese samples, almost all microbial groups showed a significant decrease during the analysed period, with the exception of Enterobacteria. It is interesting to note that Escherichia coli and Listeria spp. were not detected in any cheese sample investigated, confirming the cheese safety. Overall, volatile organic compounds, detected on cheese samples, decreased trough the investigated period and this behavior could be related to the feeding quality and to the milk's goat nutritional components.
Elastoplastic source model for microseismicity and acoustic emission
Authors: Minakov Alexander , Yarushina Viktoriya
Published: May 2021

The microseismic events can often be characterized by a complex non-double couple source mechanism. Recent laboratory studies recording the acoustic emission during rock deformation help connecting the components of the seismic moment tensor with the failure process. In this complementary contribution, we offer a mathematical model which can further clarify these connections. We derive the seismic moment tensor based on classical continuum mechanics and plasticity theory. The moment tensor density can be represented by the product of elastic stiffness tensor and the plastic strain tensor. This representation of seismic sources has several useful properties: (i) it accounts for incipient faulting as a microseismicity source mechanism, (ii) it does not require a pre-defined fracture geometry, (iii) it accounts for both shear and volumetric source mechanisms, (iv) it is valid for general heterogeneous and anisotropic rocks and (v) it is consistent with elasto-plastic geomechanical simulators. We illustrate the new approach using 2-D numerical examples of seismicity associated with cylindrical openings, analogous to wellbore, tunnel or fluid-rich conduit and provide a simple analytic expression of the moment density tensor. We compare our simulation results with previously published data from laboratory and field experiments. We consider four special cases corresponding to ‘dry’ elastically homogeneous and elastically heterogeneous isotropic rocks, ‘dry’ transversely isotropic rocks and ‘wet’ isotropic rocks. The model highlights theoretical links between stress state, geomechanical parameters and conventional representations of the moment tensor such as Hudson source type parameters.
Surgical management of an aortic root dilatation in a patient suffering from Hunter syndrome
Authors: Poitier Bastien , Amrane Mourad , Bruneval Patrick , Achouh Paul
Published: May 2021

Hunter syndrome is a rare disease leading to glycosaminoglycan accumulation in tissues. Multiple organs are involved, but prognosis is mainly conditioned by cardiac and respiratory failures. Cardiac valvular impairment is quite common but aortic root dilatation is rarely described. This article covers a case of surgical root replacement due to aortic valve insufficiency and aortic root dilatation documented with magnetic resonance and computed tomography angiographies. Anatomic pathology reported both aortic valve and aorta with mucoid overload and elastic fibre depletion. These patients do have a risk of aortic root dilatation, which justifies periodic monitoring. Diagnosis must be made using indexed measures.
Constructing Non-Semisimple Modular Categories With Relative Monoidal Centers
Authors: Laugwitz Robert , Walton Chelsea
Published: May 2021

This paper is a contribution to the construction of non-semisimple modular categories. We establish when Müger centralizers inside non-semisimple modular categories are also modular. As a consequence, we obtain conditions under which relative monoidal centers give (non-semisimple) modular categories, and we also show that examples include representation categories of small quantum groups. We further derive conditions under which representations of more general quantum groups, braided Drinfeld doubles of Nichols algebras of diagonal type, give (non-semisimple) modular categories.
The Case of (Digital) Wagner
Authors: Kivy Peter
Published: May 2021

The article argues that the proposal to produce a digital Ring cycle was not just ethically and economically misguided, but aesthetically misguided as well. Orchestras produces performances, and the proposed digital Ring would not have produced genuine performances of the Ring operas. Nevertheless, a digital musical work might allow us to reconstruct, and in that way recover and gain access to, a full-fledged musical work.