bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute hemodynamic response of epicardial and endocardial cardiac resynchronization therapy, His bundle pacing and left bundle branch pacing
Authors: Elliott MK , Strocchi M , Sidhu BS , Mehta V , Porter B , Gould J , Niederer S , Rinaldi CA
Published: May 2021

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Medtronic

Background / Introduction

Endocardial pacing and conduction system pacing are emerging as alternative methods to deliver cardiac resynchronization therapy (CRT) and have been shown to achieve superior acute hemodynamic response (AHR) compared to conventional epicardial pacing. However, a direct comparison of all the methods of delivering CRT has not yet been performed.

Purpose

To directly compare the AHR of conventional CRT (BiV Epi), endocardial pacing (BiV Endo), His bundle pacing (HBP) and left bundle branch pacing (LBBP) during a temporary CRT study.

Methods

4 patients underwent a temporary CRT and hemodynamic study. Temporary pacing was achieved using quadripolar catheters in the right atrium and coronary sinus, and roving decapolar catheters in the right ventricle (RV) and left ventricle (LV) via retrograde aortic access. Hemodynamic assessment was performed with a PressureWire X (Abbott, CA, USA) in the LV cavity. AHR was calculated as the percentage improvement in LV dP/dtmax from baseline AAI or RV pacing (if underlying complete heart block).

Results

The patients had a mean age of 67.5 ±5.8 years and all had non-ischemic cardiomyopathy with severe LV impairment (mean ejection fraction 22.5 ±7.4%). 3 patients had left bundle branch block and 1 patient had complete heart block with an RV paced rhythm (mean QRS duration 157 ±24 ms). All methods of delivering CRT achieved a mean AHR of >10%, which is considered clinically significant and is predictive of LV remodelling at 6 months. Mean AHR during BiV Epi pacing was 12.6 ±5.0%. There was a trend towards higher AHR for BiV Endo pacing (23.6 ±7.6%), HBP (17.4 ± 9.5%) and LBBP (16.1 ±7.8%) as shown in figure 1, however there was no significant difference between groups on one-way analysis of variance (p = 0.348).

Conclusions

All methods of delivering CRT achieved an AHR >10%. The AHR during BiV Endo pacing, HBP and LBBP was higher than for BiV Epi pacing, but this did not reach statistical significance. Further investigation with larger studies is required to determine which method of delivering CRT achieves the best hemodynamic response.

Figure 1. Box plot of acute hemodynamic response (AHR) for conventional cardiac resynchronization therapy (BiV Epi), endocardial pacing (BiV Endo), His bundle pacing (HBP) and left bundle branch pacing (LBBP). Data displayed as median (solid line), mean (+), 1st and 3rd quartiles (box) and minimum and maximum values (whiskers). Abstract Figure 1
Outcomes and predictors of clinical response after upgrade to resynchronization therapy
Authors: Brandao M , Goncalves Almeida J , Fonseca P , Rosas F , Santos E , Ribeiro J , Oliveira M , Goncalves H , Fontes-Carvalho R , Primo J
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

BACKGROUND

 Upgrade to  resynchronization therapy (CRT) is common practice in Europe. However, patient selection remains a challenge. Data regarding predictors of response to upgrade is currently lacking.

AIM

To identify predictors of clinical response after upgrade to CRT.

METHODS

Single-center retrospective study of consecutive patients submitted to upgrade to CRT (2007-2018). Patients underwent clinical and echocardiographic (echo) evaluation at baseline, 6-months and 1-year. Major adverse cardiac events (MACE) included hospitalization for heart failure (HF) or all-cause mortality. Clinical response was defined as New York Heart Association (NYHA) class improvement without MACE in the 1st year of follow-up (FU). Left ventricle end-systolic volume reduction of >15% designated echo response. Multivariate logistic regression was performed to identify predictors of clinical response to CRT.

RESULTS

Fifty-six patients submitted to upgrade to CRT (80.4% male, mean age 70.0 ± 9.6 years) were included; 43 patients (78.2%) previously had a pacemaker and 12 (21.8%) had a defibrillator device.  Most patients had non-ischemic HF (67.9%), with a mean baseline left ventricle (LV) ejection fraction of 27.9 ± 6.4%. Indications for upgrade were mainly pacemaker dependency or pacing-induced LV dysfunction (76.6%) and de novo left bundle branch block (23.4%).

Thirty-one (59.3%) patients were clinical responders. MACE occurred in 37.5% of patients; 28.6% were hospitalized for HF and 13% died during the 1st year of FU. Clinical responders had a lower rate of atrial fibrillation (AF) (46.9% vs. 53.1%, p=.025) and a higher rate of pacemaker rythm prior to upgrade (80.6% vs 47.6%, p=.013). Among responders, the previous device was more frequently a pacemaker (87.5% vs 61.9%, p=.029), and the new device a CRT-P (81.2% vs 54.5%, p=.035). HF etiology did not differ between responders and non-responders.

Multivariate analysis identified absence of AF (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1-17.6, p=.037), CRT-P (OR 5.7, 95% CI 1.3-25.8, p=.022) and quadripolar lead implant (OR 3.8, 95% CI 1.3-25.8, p=.024) as predictors of clinical response in upgraded patients.

CONCLUSIONS

In this cohort, absence of AF, implantation of CRT-P and use of a quadripolar lead predicted clinical response to upgrade to CRT. Larger studies are warranted to tailor selection of patients for upgrade procedures.
NISAR-F SCORE: a simple risk stratification tool for patients implanted with cardiac resynchronization therapy
Authors: Correia J , Goncalves L , Pires I , Santos J , Neto V , Ferreira G , Costa A , Cabral J
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Individualized estimation of prognosis after cardiac resynchronization therapy (CRT) remains challenging. Outcomes in this group of patients are influenced by multiple factors and a comprehensive and customized approach to estimate prognosis after CRT is lacking

Aims

To develop and validate a simple prognostic score for patients implanted with CRT (NISAR-F score), based on readily available clinical and echocardiographic variables to predict the combined endpoints of death or hospitalization in 24 months.

Methods

A single-centre retrospective study was conducted with inclusion of all consecutive patients who underwent CRT implantation between 2012 and 2019. Follow-up started after CRT implantation and ended upon death, hospitalization or 24 months after study entry. Survival analysis was performed using a multivariate Cox regression model, in order to analyze the effect on survival /hospitalization in 24 months of the following factors: age, gender, NYHA Class III-IV, ischemic heart failure, type 2 diabetes, arterial hypertension, dyslipidemia and ejection fraction < 21%. According to the analysis, points were attributed to each factor. Afterwards, the NISAR-F score was calculated for each patient, summing the points of each variable. The authors finally created ROC curves for the NISAR-F score to predict the occurrence of the combined endpoint in 2 groups of patients: CRT responders (ejection fraction increase of at least 10% after CRT implantation) and CRT non-responders. The statistical analysis was performed in SPSS.

Results

102 patients were included in the study (75.4% male, mean age 68 ± 10.46 years). 10(9.8%) of the patients were re-hospitalized and 8 (7.8%) died during the 24-month follow-up.  After calculating NISAR-F score for each patient, area under ROC curves were obtained. The analysis of the ROC curves allows us to confirm the good performance of the score created [responders group (AUC 0.812) vs non-responders (AUC 0.721)].

Conclusion The NISAR-F score is a useful tool to predict the combined endpoint (mortality and hospitalization in 24 months) after CRT implantation, in both responders and non-responders, revealing good performance of this new and simple score based only on clinical and echocardiographic variables.
Electrocardiographic pattern in V1, aVL and I as predictor of events in heart failure following cardiac resincronization
Authors: Asensio Nogueira J , Salgado-Aranda R , Garcia-Fernandez FJ , Martin-Gonzalez FJ , Villagraz-Tecedor L , Gomez-Llorente M , Alvarez-Calderon M , Fernandez-Gonzalez B , Sanchez-Corral E , Perez-Rivera JA
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

following cardiac resincronization therapy (CRT), QRS duration is the most important prognostic factor in the 12-lead electrocardiogram (ECG). However, there is little evidence regarding if the electrocardiographic pattern following CRT has impact on morbidity and mortality.

Purpose

In this historical cohort study we analysed if a certain pattern in three leads of the ECG (Rs in V1, Qr in aVL or rS in I) is associated with lower incidence of adverse outcomes in a population of CRT patients within 1 year of implant. Other variables previously associated with success or failure of CRT were analysed.

Methods

patients with CRT devices with left ventricle lead in the coronary sinus were included from January 2012 to April 2019. The primary endpoint was a composite of death of any cause and heart failure hospitalization at 1 year. Survival analysis was performed using Kaplan-Meier test, comparing survival graphics through Log-Rank test. For multivariate analysis, Cox regression was performed.

Results

111 patients were included. Sample was divided into 2 groups according to the presence of the pattern in any of the three ECG leads. Baseline characteristics are reported in Table 1. Presence of any of the three patterns was independently associated with a lower incidence of the primary endpoint (2.3% vs. 17.6%, hazard ratio 0.1, 95% confidence interval 0.013-0.774, p = 0.016). Previous atrial fibrillation was also independently associated with a higher incidence of the primary endpoint. QRS duration postimplantation did not showed prognostic value.

Conclusion

the presence of the patterns Rs in V1, Qr in aVL or rS in I is an independent predictor of good prognosis in patients with CRT. Baseline characteristicsPattern Rs-V1/Qr-aVL/rS-INo patternp-valueAge (years)69 ± 1767 ± 210.257Women8 (18.6)17 (25)0.432Atrial fibrillation18 (41.9)22 (32.4)0.309- Ischemic cardiomyopathy- Non ischemic cardiomyopathy18 (41.9)25 (58.1)26 (38.8)41 (61.2)0.75Indication- HFrEF + NYHA II-IV + wide QRS- rEF + indication of cardiac stimulation- LV dysfunction secondary to stimulation 35 (81.4)7 (16.3)1 (2.3) 58 (85.3)9 (13.2)1 (1.5) 0.5870.6560.741Preimplantation LVEF (%)28 ± 1328 ± 150.882Up-titrated treatment17 (39.5)26 (38.2)0.891- LBBB- RBBB36 (83.7)5 (11.6)61 (89.7)6 (8.8)0.3550.63QRS duration postimplantation (ms)144 ± 35142 ± 500.657HFrEFheart failure with reduced ejection fraction; NYHA: New York Heart Association; rEF: reduced ejection fraction; LV: left ventricle; LVEF: left ventricle ejection fraction; LBBB: left bundle branch block; RBBB: right bundle branch block.Abstract Figure. Kaplan Meier survival curves
Relationship between left bundle branch block mechanical patterns and super-response to cardiac resynchronization therapy in patients with congestive heart failure
Authors: Shirokov N , Kuznetsov V , Todosiichuk V , Soldatova A , Krinochkin D
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Left bundle branch block (LBBB) assessed by electrocardiography (ECG) is used in current clinical guidelines for patient selection to cardiac resynchronisation therapy (CRT). But percentage of non-responders among patients with congestive heart failure is high. Super-response (SR) to CRT was not enough described in clinical guidelines. We hypothesized that mechanical patterns of LBBB and parameters of mechanical dyssynchrony could be used as predictors of SR to CRT.

Aim

To assess a relationship of LBBB patterns defined by ECG and echocardiography with SR to CRT.

Materials and methods

60 patients (mean age 54.5 ± 10.4 years) were examined at baseline and during follow-up: 10.6 ± 3.6 months. Patients were divided into groups: I group (n = 31) with decrease of left ventricular end-systolic volume (ESV) ≥30% (super-responders) and II group (n = 29) - decrease of LV ESV <30% (non-super-responders). Three strain-markers of LBBB assessed by Tissue Doppler Imaging (TDI) and Speckle Tracking Echocardiography (STE) were used: (1) early contraction of basal or midventricular segment in the septal wall and early stretching of basal or midventricular segment in the lateral wall (yellow arrows); (2) the early peak contraction of the septal wall occurred in the first 70% of the systolic ejection phase (blue arrow); (3) the early stretching wall that showed peak contraction after aortic valve closure (red arrows). The classic LBBB pattern was defined if all three strain-markers were present. The heterogeneous LBBB pattern was defined if two from three strain-markers were present.

Results

At baseline groups did not differ in main clinical characteristics, including QRS width and LBBB assessed by ECG. Mechanical abnormalities were found only in group I: SF (32.3% vs 0.0%; p = 0.001) and apical rocking (19.4% vs 0.0%; p = 0.024), as well as classic LBBB mechanical pattern (20.8% vs 0.0%; p = 0.05). The complex of heterogeneous LBBB mechanical pattern (HR 7.512; 95% CI 1.434 – 39.632; р=0.025), interventricular mechanical delay (HR 1.037; 95% CI 1.005 – 1.071; р=0.017) and longitudinal strain of interventricular septum mid segment (HR 0.726; 95% CI 0.540 – 0.977; р=0.035) had an independent relationship with SR. According to the ROC analysis the sensitivity and specificity of model in the prediction of SR were 77.3% and 91.3% (AUC = 0.862; p < 0.001).

Conclusion

SR is associated with both LBBB mechanical patterns assessed by STE and TDI. LBBB defined by ECG did not have significant association with SR to CRT. Abstract Figure.
Last before-death transmission in patients with heart failure and implantable cardioverter-defibrillator followed by remote monitoring - insights from the COMMIT-HF registry
Authors: Dyrbus M , Tajstra M , Pyka L , Kurek A , Gasior M
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background 

Remote monitoring (RM) of cardiac implantable electronic devices (CIED) in patients with heart failure allows to regularly analyze the devices" and patients" conditions. 

Purpose 

The purpose of this study was evaluation of the ultimate transmissions sent before death in patients monitored remotely. 

Methods 

The last transmissions delivered by the devices in patients enrolled into COMMIT-HF Registry (NCT02536443) who died when monitored remotely have been retrospectively analysed. The characteristics and contents of the transmissions and clinical reactions undertaken have been obtained from the RM systems of four major RM providers. 

Results 

Of 1,306 patients with CIEDs who were enrolled at the RM programme in our centre, 267 died and their last transmission occurred less than 90 days before death, of which 133 (49.8%) were scheduled and 134 (50.2%) alert-triggered. The median period between transmission and death was 31 days for scheduled and 8 days for alert-triggered transmissions. The most frequent alert-triggered transmissions were atrial fibrillation/flutter (35.8%) and ventricular tachyarrhythmias (24.6%). A clinical reaction has been undertaken after 9.8% of planned and 67.1% of alert-triggered transmissions and consisted mainly of telephone consultations and referrals for hospital admissions. 

Conclusions 

This is the first analysis of the ultimate transmissions delivered by CIEDs before death. In approximately 50% of patients, the last transmission has been alert-triggered. Hence, an appropriate organization of the RM facility, which should immediately analyse and react to the transmission, seems mandatory to obtain clinical benefit in patients with HF and RM. Causes of alerts and clinical reactionsCause of alertAll alert-triggered transmissions (N = 134)AF/AFL episode, n (%)48 (35.8%)Ventricular tachycardia, n (%)18 (13.4%)Ventricular fibrillation, n (%)15 (11.2%)Biventricular pacing percentage reduction, n (%)15 (11.2%)Others38 (28.3%)Congestion monitor indications, n (%)14 (10.4%)Clinical reactionPlanned transmission (N = 133)Alert-triggered transmission (N = 134)Telephone consultation10 (7.5%)58 (43.2%)Referral to the GP or outpatient specialist clinic visit2 (1.5%)12 (8.9%)Referral for hospital admission1 (0.7%)18 (13.4%)Pharmacotherapy modificationN/A2 (1.5%)Abstract Figure.
Impact of the Covid-19 related lockdown on physical activity, heart rate and arrhythmia burden in a large prospective cohort of CHF patients
Authors: Schmitt J , De Sousa J , Bulava A , Golovchiner G , Hatala R , Anguera I , Reinke F , Wenzel B , Noelker G
Published: May 2021

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): BIOTRONIK SE & Co. KG

OnBehalf

BIO|STREAM.HF

Background

At the beginning of the Covid-19 pandemic in spring 2020, governments around the world issued curfews and other stay at home orders (‘lockdown’) to limit the spread of the SARS-CoV19 virus. This may have forced people to decrease their physical activity. Physical inactivity as well as social stress is known to be especially deleterious for heart failure (HF) patients. The BIO|STREAM.HF study enrolled such HF patients into a prospective registry with Home Monitoring.

Purpose

We aimed to evaluate the impact of the lockdown during the first Covid-19 pandemic wave on physical activity and arrhythmia burden of heart failure patients.

Methods

We analysed daily transmitted data of patients enrolled into a large international registry (BIO|STREAM.HF) being implanted with a cardiac resynchronization therapy (CRT) devices. Patients with NYHA ≥ II and LVEF ≤ 40% before CRT implantation were selected.

Intra-individual weekly mean and median values were calculated for the following daily transmitted parameters: physical activity (measured as % of the day during which the patient moves), atrial arrhythmia burden, mean heart rate (at rest), PP variability, PVC burden, and rate of biventricular pacing. Values were calculated for 12 weeks before and 12 weeks after the country-specific effective date of most rigorous restrictions in spring 2020 to visualize the general trend of parameter changes. Moreover, values for intra-individual changes between three 28-days periods (before, during, and after the lockdown) were calculated.

Results

Of 444 patients, 76% were male. They had a mean age of 69 ± 10 years and LVEF of 28.2 ± 6.7%. HF was of ischemic etiology in 42% of cases and they were in NYHA class II (47.5%), III (50.0%) or IV (2.5%).

On average, patients were active for 9% of the day (2 h 10 min). The physical activity decreased by approx. 10% with the onset of the lockdown (figure 1) and recovered within the following eight weeks.

Comparison of the 28-days periods before, during and after the lockdown showed a statistically significant intra-individual decrease in physical activity (mean decrease 9 min per day) during the lockdown compared to pre- and post-lockdown values and a trend toward reduced mean heart rates. In parallel, a significant increase in device detected atrial arrhythmia burden (mean increase 17 min per day) was observed. All other parameters did not change significantly.

Conclusion 

Our results show that patients reduced their physical activity during the Covid-19 related lockdown in spring 2020. This was associated with an increase in atrial arrhythmia burden and a reduction of the mean heart rate. Prognostic implications of these results will further be analysed. Abstract Figure.
CIED guided HF management : a prospective cohort study
Authors: Garner D , Leung WY , Llewellyn J , Goode R , Lunt L , Hughes S , Kahn M , Wright DJ , Rao A
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): Liverpool Clinical Commissioning Group

Background

Heart failure (HF) is associated with significant morbidity and mortality. (1) Cardiac Implantable Electronic Devices (CIED) generated Heart Failure Risk Score (HFRS) alerts may guide management in this complex cohort and help direct resources to appropriate patients. (2)

Aim 

To develop and evaluate an integrated, multidisciplinary approach to HF management for patients with CIED by sharing HFRS alerts directly with the HF teams.

Methods

We undertook a prospective, single centre cohort study of patients who generated high risk HFRS alerts. These alerts were shared with community HF teams responsible for routine care of patient, prompting patient contact and appropriate intervention by the team. Impact of the pathway was evaluated by review of outcomes including hospitalisation and clinical intervention within 4- 6 weeks of the alert and mortality during the follow up period. Ongoing education was provided to help teams deal with alerts. A validated user questionnaire was completed by the stake holders to obtain user feedback.

Results

365 "High risk" alerts were noted in 188 patients in a 2 year period (November 2018 - November 2020). The mean number of alerts per patients was 1.9 and 44 (23%) of patients had >3 "high risk" alerts in the follow up period. Having three or more alerts significantly increased the risk of hospitalisation for heart failure (HR 2.5, CI 1.1–5.6 p = 0.03) but not mortality (HR 2.1 CI 0.6-7.2 p = 0.23). Overall 75 (39%) of patients were hospitalised in the 4-6 week period of the alert – 53 (28%) of these were unplanned of which 24(13%) were for decompensated HF. A further 24(13%) had planned admissions for care to improve therapy (AV node ablation, device and lead replacement) and reduce morbidity (LA appendage occlude, IV Iron therapy). 33(18%) of patients died in the follow up period.  15(8%) received therapy from the device. 18(10%) of patient underwent deactivation of ICD therapy.

Contact was established in 176 (94%) of patients, and alerts actioned appropriately. 55 patients reported being asymptomatic, and in 45 the trends were improving so no further clinical action was taken. 76 patients had an onward referral made for further management including; 32 to a Cardiologist, 20 to primary care, 13 referrals to community HF teams and 11 referrals to palliative care. 23 patients had medications changes instituted. The feedback on the pathway was positive. 

Conclusions 

An integrated approach to HF for patients with CIEDs in situ can facilitate timely risk stratification and intervention in this cohort of patients and potentially reduce unplanned health care utilisation. Intervention in these patients is not limited to HF alone and provides the opportunity for holistic management of this complex cohort Abstract Figure.
Monitoring of QTc interval in patients with COVID-19. First experience with a portable EKG-recording device
Authors: Abellas Sequeiros M , Lozano Granero C , Garcia Sebastian C , Franco Diez E , Hernandez Madrid A , Moreno Planas J , Sanmartin M , Zamorano JL
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Off-label use of drugs with potential for QT interval prolongation was common in COVID-19 patients. We tested a portable EKG recording device to measure and monitor corrected QT (QTc) intervals in a cohort of COVID-19 patients treated with azithromycin, hydroxychloroquine, lopinavir/ritonavir, or combinations of these drugs.

Methods and results

Sixty-nine patients hospitalized with pneumonia and confirmed SARS-CoV 2 infection were included in an observational single-centre study. Six-lead EKG recordings were obtained using a KardiaMobile6L® at physicians’ discretion. In a subgroup of 16 patients with early discharge, a device was provided for at-home daily monitoring. Significant QTc interval prolongation was observed in patients taking a combination of 2 or 3 drugs (426 ± 33 vs 408 ± 33 ms, p = 0,002; and 435 ± 30 vs 394 ± 31 ms, p = 0,001, respectively). The use of the device prompted a change in the treatment of 9 patients (13%) because of prolongation of QTc interval and anticoagulation was started in one patient because of atrial fibrillation diagnosis. In the subgroup of patients with daily recording, QTc interval prolongation peaked at day 2 ± 1,8, with a shorter final QT interval than that recorded before drug initiation (350,0 ± 31,4 vs 381,0 ± 21,2; p = 0,019), pointing to a possible role of the disease itself in QT interval modification.

To assess the consistency of measurements of QTc interval, a random sample of 120 EKG recordings were analyzed by two different physicians. Inter-operator intraclass correlation coefficient was 0,702, 95% CI (0,578-0,789).

Conclusions

Portable EKG-recording device was useful for QTc interval monitoring in COVID-19 patients receiving drugs with QTc prolonging potential, allowing physicians to adapt management. Significant QT prolongation was observed in these patients. Characteristics of the three groups.Group 1(one drug)N= 9 (13,0%)Group 2(two drugs)N= 37 (53,6%)Group 3(three drugs)N= 23 (33,3%)p-valueClinical characteristicsAge (years)55,0 ± 18,366,0 ± 16,258,0 ± 15,8p = 0,248Male sex (%)6 (66,7%)25 (67,6%)18 (78,3%)p = 0,643Dislipidaemia (%)5 (55,6%)9 (24,3%)7 (30,4%)p = 0,749Diabetes (%)7 (77,8%)4 (10,8%)5 (21,7%)p = 0,525Hypertension (%)3 (33,3%)16 (43,2%)8 (34,8%)p = 0,387Previous cardiopathy (%)6 (66,7%)11 (29,7%)3 (13,0%)p = 0,305COPD (%)7 (77,8%)6 (16,2%)1 (8,7%)p = 0,679COPDchronic obstructive pulmonary disease.Abstract Figure. Baseline and maximum QTc intervals
Virtual reality to improve patient information and reduce anxiety towards atrial fibrillation ablation in times of remote patient care (and after)
Authors: Hermans ANL , Van Duijnhoven P , Verhaert DVM , Philippens S , Lahaije M , Clerx K , Debie L , Den Uijl DW , Vernooy K , Linz D , Weijs B
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Background. Nowadays frequently deployed invasive catheter ablation therapy in patients with symptomatic atrial fibrillation (AF) is unfortunately associated with distress such as preoperative anxiety. Improving preoperative patient information may lower anxiety towards AF ablation procedures.

Purpose. To evaluate whether a lifelike 360˚ virtual reality (VR) patient information video decreases anxiety levels and improves patient preparation towards AF ablation as compared to standard preoperative patient information.

Methods. Consecutive patients planned for AF ablation were recruited from the outpatient AF clinic and were randomized into two groups: the control group and the intervention group (VR group). The control group received standard preoperative information through oral counselling and information leaflets, the VR group received the standard information as well as a short dedicated 360˚ VR video (via in-hospital VR headset and disposable cardboard VR glasses for home use). Online questionnaires (aimed at information provision, anxiety and procedural experience) were administered both pre- and post-ablation.

Results. A total of 103 patients (39.8% female, age 64 [58-71] years) were included in the analysis. The VR group (n = 58) reported to be clearly better informed about catheterization laboratory environment (78% vs. 73%) and the course of the procedure (82% vs. 78%), indicated fewer concerns about the procedure (47% vs. 55%) and were eager to learn even more (82% vs. 74%) as compared to controls (n = 45). However, there was no significant difference in the anxiety scores between the VR group and controls (10 [8-12] vs. 10 [8-14], p = 0.548). Home use of the video was satisfactory and resulted in discussion with relatives. Patient overall satisfaction was higher in VR group as compared to controls (84% vs. 81%).

Conclusions. This study shows that a dedicated 360˚ VR video reduces concerns but does not reduce anxiety scores. Though, it easily improves procedural knowledge, patient information and patient satisfaction. Especially in times of remote patient care, this new way of informing patients may be of added value.
Desmosomal vulnerability renders left atria more susceptible to detrimental effects of androgenic anabolic steroids
Authors: Sommerfeld L , Holmes AP , Kavanagh DM , Pike JA , O Shea C , Cardoso VR , Kabir SN , Pavlovic D , Gehmlich K , Stoll M , Gkoutos GV , Kirchhof P , Fabritz L
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): CATCH ME Foundation Leducq

BACKGROUND

In cardiac myocytes, desmosomal proteins and ion channels form macromolecular complexes important for maintaining cell adhesion and electrical integrity. High serum levels of androgenic anabolic steroids (AAS) promote cardiac muscle growth, but any detrimental impact on atrial gene transcription and/or electrophysiological function is unknown.

PURPOSE

To investigate the effects of chronic AAS exposure on atria in a mouse model with desmosomal impairment.

METHODS

Young (8-10 week) male wild-type (WT) and heterozygous plakoglobin-deficient (plako+/-) mice were challenged with the AAS dihydrotestosterone (DHT) or placebo for 6 weeks by osmotic mini pumps. RNA sequencing (n = 3-6 atria/group) revealed effects of genotype and DHT on left atrial (LA) transcription. Membrane-localised cardiac sodium channels (Nav1.5) were visualised using direct STochastic Optical Reconstruction Microscopy (dSTORM, n = 5-11 LA/group, 122 cells in total) and clustering of individual molecules was quantified using persistence-based clustering. Patch clamping of LA cardiac myocytes was used to record whole cell sodium currents (n = 4-5 LA/group, 77 cells in total). LA action potentials and conduction velocity were evaluated using microelectrode and optical mapping techniques (n = 5-9 LA/group).

RESULTS

DHT increased expression of pro-hypertrophic transcripts, e.g. Igf1, Mtpn, fibrosis-associated transcripts, e.g. Col1a1, Col3a1, Lox and pro-inflammatory transcripts, e.g. Ccl6, C7, in both WT and plako+/- LA. Despite Scn5a transcript levels being maintained, dSTORM identified a 29% reduction (p = 0.042) in the number of Nav1.5 localisations at the membrane of plako+/- DHT LA cardiomyocytes, and 25% fewer localisations (p = 0.005) were found within Nav1.5 clusters, compared to WT DHT. Electrophysiological methods revealed a significant reduction in peak sodium current density, decreased action potential amplitude and conduction slowing in plako+/- LA after exposure to DHT.

CONCLUSION

This data suggests that a reduction in plakoglobin expression predisposes atrial cardiomyocytes to detrimental electrophysiological effects of high testosterone levels. This is characterised by a perturbed spatial organisation of Nav1.5, decreased sodium current density and conduction slowing. Abstract Figure. Abstract Picture
Impact of epicardial fat on the duration of radiofrequency energydelivery during catheter ablation of atrial fibrillation
Authors: Oudin V , Marcus C , Faroux L , Espinosa M , Metz D , Lesaffre F
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Aims

This study aimed to determine the impact of the volume of epicardial fat on the duration of radiofrequency (RF) energy delivery during the procedure of ablation of atrial fibrillation (AF).

Methods

The volume of epicardial fat was measured from spiral computerized tomography scan. The primary endpoint was the duration of RF delivery for pulmonary vein isolation (PVI), and the overall total duration of RF application. Secondary endpoint was conversion of AF to sinus rhythm or organisation of the arrhythmia after PVI.

Results

From March 2015 to May 2018, 222 patients (45,5% with persistent AF) underwent a first RF catheter ablation procedure for AF. The total duration of RF delivery, and the duration of RF delivery specifically for PVI were significantly associated with higher total volume of epicardial fat (p = 0,0002; p = 0,009 respectively), periatrial (p = 0,003; p = 0,045) and periventricular epicardial fat (p = 0,001; p = 0,012). In multivariate analysis, total epicardial fat volume was not significantly associated with total RF delivery duration (p = 0,743). For patients with arrhythmia at the time of the procedure, patients who achieved conversion or organisation of their arrhythmia after PVI had similar levels of total epicardial fat to those whose arrhythmia persisted (65 ± 35,2 vs 74,5 ± 31,2 ml ; p = 0,192).

Conclusion We observed a significant relation between total, periatrial, and periventricular epicardial fat, and the duration of RF delivery during ablation of AF. This relation was not significant by multivariate analysis meaning that epicardial fat maybe a marker, but not an independent factor,of ablation complexity.
Autonomous initiation of pacemaking by L-type Cav1.3 calcium channels in mouse sino-atrial myocytes
Authors: Louradour J , Bidaud I , Le Guennec JY , Mangoni M , Mesirca P
Published: May 2021

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): Ecole doctorale

Background

Cardiac pacemaking relies on the spontaneous electrical activity in the right atrium of sino-atrial myocytes (SANCs). Automaticity in SANCs results from a robust interplay of membrane ion channels activity and intracellular calcium dynamics. However, only a fraction of isolated SANCs exhibit rhythmic firing, whereas most SANCs show irregular (dysrhythmic) firing or remain dormant.

Purpose

To study the capability of L-type Cav1.3 calcium channels to initiate automaticity in dormant SANCs under β-adrenergic stimulation, we used a knock-in mouse strain in which the sensitivity of Cav1.2 α1 subunits to dihydropyridines (DHP) was inactivated (Cav1.2DHP-/-).

Methods

We performed current and voltage-clamp recordings on isolated SANCs under isoprenaline (ISO, 100 nM) and in the absence or presence of the DHP blocker Nifedipine (Nife, 3 µM).

Results

Nife significantly reduced the spontaneous firing under ISO perfusion in all rhythmic SANCs (ISO: 447 ± 12, ISO + Nife: 233 ± 25 bpm) and 60% of dysrhythmic SANCs (ISO: 386 ± 12, ISO + Nife: 188 ± 47 bpm) whereas it completely stopped it in the remaining 40% (295 ± 29 bpm to 0). On 25 dormant SANCs, 50% started firing after ISO perfusion (0 to 320 ± 46 bpm). Strikingly, in 75% of them, Nife totally blocked this ISO-induced firing. Interestingly, these cells exhibited a significantly slower rate and a slower slope of the diastolic depolarization under ISO perfusion compared to the remaining 25% dormant SANCs in which Nife only reduced the ISO-induced firing. Moreover, dormant SANCs showed a statistically significant increase in action potential (AP) threshold under ISO compared to dysrhythmic and rhythmic SANCs (dormant: -30.1 ± 2.5, dysrhythmic: -43.3 ± 2.3, rhythmic: -41.2 ± 2.1 mV). No significant difference was observed in the other AP parameters between dormant, dysrhythmic and rhythmic SANCs under ISO.

Conclusion

 Our results seem to point at a difference of expression in ionic channels (Cav1.3, HCN4) within isolated SANCs. Preliminary results on If density support this hypothesis with a lesser density in dormant SANCs compared to dysrhythmic SANCs. These results also tend to indicate that Cav1.3 channels can generate pacemaker activity autonomously, at least in a particular subpopulation of SANCs.
The influence of frailty syndrome on quality of life in patients with atrial fibrillation
Authors: Lomper K , Loboz-Rudnicka M , Uchmanowicz I , Jaroch J
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

 Atrial fibrillation (AF) is associated with decreased quality of life (QoL) compared to the general population and to other cardiovascular conditions. In addition, the co-occurrence of frailty syndrome (FS) affects the risk of developing adverse health outcomes including disability and rehospitalizations. This may further translate into a decreased subjective sense of QoL.

Purpose

To evaluate the prevalence of FS and its impact on subjective QoL in a group of patients with AF.

Methodology

116 patients (mean age 75.21 ± 8.19) with diagnosis of AF hospitalized at the Cardiology Department were included in the study. Medical record analysis and self-administered questionnaire were used to obtain basic sociodemographic and clinical data. The prevalence of FS was assessed using the Tilburg Frailty Indicator (TFI) questionnaire. The standardized Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) assessing quality of life was used. 

Results

FS was diagnosed in 67.24% of the patients. The group with FS was predominantly elderly (p < 0.001), female (p = 0.03), less educated (p = 0.04), single (p= <0.001), with coexisting heart failure (p = 0.015 ) and with higher EHRA classification (p = 0.014). Better QoL was demonstrated in the group of patients without FS in the total score (p = 0.004), psychological domain (p = 0.014) and physical domain (p = 0.004). There was a significant positive correlation of TFI total score with overall QoL (B = 0.383; p < 0.001) and psychological (B = 0.355; p < 0.001) and physical (B = 0.336; p < 0.001) domains.

Conclusions

FS is common in patients with AF. Assessment of FS occurrence is important for everyday clinical practice because FS lowers QoL. The consequence of FS and decreased QoL may be worse patient prognosis and increased number of hospitalizations.
Soluble ST2 and renal function in ischemic heart failure with atrial fibrillation
Authors: Lashkul D
Published: May 2021

Funding Acknowledgements

Type of funding sources: None.

Soluble ST2 (sST2) is a novel cardiac biomarker whose concentration rises in response to myocardial strain. The aim of this study was to analyse the relationship between soluble ST2 (sST2) level and renal function in heart failure (HF) patients with atrial fibrillation (AF).

Methods

The study involved 113 (83.2% men) patients with mean age 60.0 [54.0-67.0] years with II-IV functional class (recommendations of the New York Heart Association) is due to ischemic heart disease. Serum levels of N-terminal proBNP (NT-proBNP), sST2, TIMP-1 and Cystatine C (CysC) were quantified by ELISA of 33 patients with HF and AF and 80 patients with HF without AF. Echocardiography was performed according to the American Society of Echocardiography/European Association of Echocardiography recommendations. Estimated glomerular filtration rate (eGFR) was calculated by MDRD formula. Nonparametric Mann-Whitney U-test for independent data, Spearman’s rank correlation and multiple linear regression coefficients were calculated.

Results

Patients with HF and AF characterized significantly higher concentration of sST2 (1453.2 [1184.3-1945.7] vs 1279.7 [1110.9-1616.6] pg/ml, p = 0.05), as well as the marker of kidney dysfunction CysC (1375 [1111.7-1867.4] vs 1136.4 [955-1386.4] ng/ml, p = 0.02) and was significantly lower eGFR (67.7 [60.6-77.2] vs 79.3 [70.9-88.0] ml/min/1.73m2; p = 0.0002). sST2 correlated with TIMP-1 (r = 0.56; p = 0.004) E/e’ (r = 0.87; p = 0.002), as well as CysC with NT-proBNP (r = 0.56; p = 0.002), with age (r = 0.49; p = 0.009) in patients with HF and AF. At multivariate linear regression analysis, only TIMP-1 (β=0.63) and left atrial volume index (β=0.22) were independently associated with sST2 (R2 = 0.58; p = 0.002).

Conclusions

In patients with ischemic HF and atrial fibrillation elevation sST2, associated with high level cystatine C and correlated with TIMP-1, E/e’, markers which showed abnormal collagen homeostasis and significant diastolic dysfunction LV. Multivariate analysis shows, that sST2 independently associated with TIMP-1 and LAVi. Further studies are needed to clarify the prognostic role of marker renal function (CysC) and cardiovascular stress (sST2) in ischemic HF patients with atrial fibrillation.
Cholinergic regulation of cardiac pacemaker activity by L-type Cav1.3 channels
Authors: Talssi L , Bidaud I , Mangoni ME , Mesirca P
Published: May 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): Fondation Recherche Médicale

Introduction

The cholinergic regulation of heart rate (HR) is mediated by acetylcholine (ACh)-dependent activation of M2-receptors (M2R). Activated M2R promote release of the βγ-subunit of G-proteins to directly gate GIRK1/4 channels (underlying the cardiac IKACh current), while αi-subunits inhibit adenylate cyclase (AC) activity. AC inhibition reduces the intracellular concentration of cAMP, decreasing the activity of ion channels involved in pacemaking, including "funny" f-(HCN4) and L-type Cav1.3 calcium channels.

Purpose

To determine the role of L-type Cav1.3 channels in cholinergic regulation of heart rate.

Methods

We recorded the frequency of activation and position of pacemaker leading site in ex vivo sinus nodes and the HR of isolated Langendorff perfused hearts of mice at baseline or during ACh perfusion.  We used control wild type (WT) mice, and five genetically modified mouse models: Cav1.3 knockout (KO, ablated Cav1.3-mediated L-type current), GIRK4KO (ablated IKACh current), HCN4-CNBD (selective deletion of cAMP-dependent regulation of HCN4), GIRK4KO/HCN4-CNBD and GIRK4KO/Cav1.3KO. We performed in vivo telemetric recordings of heart rate (HR) in WT and GIRK4KO/Cav1.3KO animals.

Results

Data from optical mapping experiments showed that, under basal conditions, perfusion of 3 μM ACh significantly reduced the frequency of action potentials in WT (44%), HCN4-CNBD (38%), Cav1.3KO (65%) and GIRK4KO (8%) isolated mouse sinus node tissues. ACh application did not significantly affect the frequency of action potentials recorded in tissue from GIRK4KO/HCN4-CNBD and GIRK4KO/Cav1.3KO animals. Furthermore, in all sinus nodes tested, regardless of genotype, ACh shifted the pacemaker leading site from its normal position by at least 0.7 mm.

Upon stimulation of the β-adrenergic pathway by Isoproterenol, to reproduce conditions of accentuated antagonism, 3µM ACh reduced HR in isolated hearts from WT (43.8%), HCN4-CNBD (38.7%), Cav1.3KO (25,4%), GIRK4KO (16.9%) and GIRK4KO/HCN4-CNBD (16.4%) mice. No significant HR reduction was recorded in hearts from GIRK4KO/Cav1.3KO animals.

In vivo data indicate that HR reduction induced by combined injection of Hexamethonium ( a Nicotinic acetylcholine receptor blocker) with Carbamoylcholine (CCH, M2 receptor agonist) or with 2-Chloro-N6-Cyclopentyladenosine (CCPA, A1 receptor agonist) is higher in WT than in GIRK4KO/Cav1.3KO animals (68% vs 48% CCH, and 79% vs 62% CCPA, respectively).

Conclusion

Our data indicate that L-type Cav1.3 channels are involved in cholinergic regulation of heart rate in mice. In addition, when the intracellular concentration of cAMP is elevated (i.e. under conditions of accentuated antagonism), cholinergic regulation of sinus node pacemaking is reliant on Cav1.3 and KACh channels.
The lectin LecA sensitizes the human stretch-activated channel TREK-1 but not Piezo1 and binds selectively to cardiac non-myocytes
Authors: Darkow E , Rog-Zielinska EA , Madl J , Brandel A , Siukstaite L , Omidvar R , Kohl P , Ravens U , Roemer W , Peyronnet R
Published: May 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research was supported by the European Research Council (Advanced Grant CardioNECT, Project ID: #323099, PK) and a research grant from the Ministry of Science, Research and Arts Baden-Württemberg (MWK-BW Sonderlinie Medizin, #3091311631).

Mechanical stimuli are detected and transduced by cellular mechano-sensors, including stretch-activated ion channels (SAC). SAC are activated by stretch and changes in membrane curvature but their precise role in the heart is unclear.

The lectin LecA is a virulence factor of Pseudomonas aeruginosa and essential for bacterial cell invasion by inducing membrane curvature. We investigate whether LecA modulates SAC activity, namely TREK-1 and Piezo1 in human embryonic kidney (HEK) cells.

Confocal microscopy and electron tomography were used to follow binding dynamics of LecA, and the ion channel activity was recorded using the patch-clamp technique. Additionally, freshly isolated cardiac cells were used for studies into cell type dependency of LecA binding.

LecA binds within seconds to cell surface. Local plasma membrane invaginations are detected by 17 min of LecA exposure. LecA sensitizes TREK-1, but not Piezo1, to voltage and mechanical stimulation. In freshly isolated cardiac cells, LecA binds to non-myocytes, but not to cardiomyocytes from mouse, rabbit, pig, and human.

Our results suggest that LecA may serve as a pharmacological tool to study cardiac SAC in a cell type-preferential manner. Abstract Figure. Graphical abstract
Catalase inhibition by nitric oxide potentiates hydrogen peroxide to trigger catastrophic chromosome fragmentation in Escherichia coli
Authors: Agashe Pooja , Kuzminov Andrei
Published: May 2021

Hydrogen peroxide (H2O2, HP) is a universal toxin that organisms deploy to kill competing or invading cells. Bactericidal action of H2O2 presents several questions. First, the lethal H2O2 concentrations in bacterial cultures are 1000x higher than, for example, those calculated for the phagosome. Second, H2O2-alone kills bacteria in cultures either by mode-one, via iron-mediated chromosomal damage, or by mode-two, via unknown targets, but the killing mode in phagosomes is unclear. Third, phagosomal H2O2 toxicity is enhanced by production of nitric oxide (NO), but in vitro studies disagree: some show NO synergy with H2O2 antimicrobial action, others instead report alleviation. To investigate this “NO paradox,” we treated Escherichia coli with various concentrations of H2O2-alone or H2O2+NO, measuring survival and chromosome stability. We found that all NO concentrations make sublethal H2O2 treatments highly lethal, via triggering catastrophic chromosome fragmentation (mode-one killing). Yet, NO-alone is not lethal, potentiating H2O2 toxicity by blocking H2O2 scavenging in cultures. Catalases represent obvious targets of NO inhibition, and catalase-deficient mutants are indeed killed equally by H2O2-alone or H2O2+NO treatments, also showing similar levels of chromosome fragmentation. Interestingly, iron chelation blocks chromosome fragmentation in catalase-deficient mutants without blocking H2O2-alone lethality, indicating mode-two killing. In fact, mode-two killing of WT cells by much higher H2O2 concentrations is transiently alleviated by NO, reproducing the “NO paradox.” We conclude that NO potentiates H2O2 toxicity by promoting mode-one killing (via catastrophic chromosome fragmentation) by otherwise static low H2O2 concentrations, while transiently suppressing mode-two killing by immediately lethal high H2O2 concentrations.
Retroperitoneal necrotizing fasciitis with the involvement of the anterior abdominal wall following perianal abscess
Authors: Abebe Metasebia W , Nigussie Mary Mesfin
Published: May 2021

Necrotizing fasciitis (NF) is a life-threatening infection, which requires immediate debridement and broad-spectrum antibiotic treatment. Delay in prompt diagnosis and operative debridement is associated with significant morbidity and mortality. Retroperitoneal NF is a rare condition whereby the infection within the pelvis or retroperitoneum rapidly expands over the fascial planes to involve the anterior abdominal wall (AW), the thighs and the buttocks. It presents a challenge for surgical access due to the anatomic depth of the structures and may result in extensive soft tissue loss requiring complex AW reconstruction for closure. The case discussed here is a 43-year-old female with a perianal abscess that progressed to retroperitoneal and anterior AW NF with intra-peritoneal abscess collection requiring bilateral tensor fascia-lata graft for the closure of the anterior AW fascia defect.