bluuebunny/crossref_metadata_2025 huggingface dataset:
Endomyocardial biopsy: what future in arrhythmogenic right ventricular dysplasia diagnosis?
Authors: Maragna R , Trombara F , Frappampina A , Dello Russo A , Gasperetti A , Catto V , Conte E , Vettor G , Sicuso R , Sommariva E , Natale A , Andreini D , Basso C , Tondo C , Casella M
Published: November 2020

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its diagnosis is challenging and the role of endomyocardial biopsy (EMB) is controversial and has been recently questioned.

Purpose

We aimed to 1) analyse the role of EMB in improving the diagnostic performance of 2010 Task Force Criteria (TFC) in the diagnosis of ARVC; 2) assess EMB safety in our population.

Methods

We retrospectively analysed data from 54 consecutive patients admitted to our Hospital with a clinical suspicion of ARVC undergoing endomyocardial biopsy. During hospitalization a complete assessment was performed for every patient (including electrocardiogram, echocardiogram, cardiac MRI, genetic analysis, and electroanatomic-mapping-guided endomyocardial biopsy). ARVC diagnosis was assessed for every patient using both traditional 2010 TFC and a non-invasive modified TFC (2010 TFC criteria excluding biopsy).

Results

Overall, 9/54 (17%) patients showed a left-dominant variant of ARVC and were therefore excluded from the analysis. Non-invasive modified TFC allowed 16/45 (36%) patients to receive a definite diagnosis; when biopsy results were added the number of definite diagnosis increased to 22/45 (49%), increasing the number of patients with a definite diagnosis by 13%. More specifically: 8/11 patients not reaching a possible diagnosis were reclassified as either possible (4/8) or borderline (4/8); 3/9 patients with a possible diagnosis were reclassified as borderline; 6/9 borderline patients received a definite diagnosis of ARVC. Globally, in 6 out of 29 patients with a non-definite diagnosis, EMB confirmed ARVC diagnosis and 17/45 (38%) patients received an upgrade in their diagnostic status with EMB. Notably, EMB also revealed the coexistence of myocarditis and fibro-fatty replacement in 5/45 (9%) patients. No patient experienced complications related to EMB.

Conclusions

Endomyocardial biopsy is a safe, reliable, and useful tool for ARVC diagnosis, allowing to upgrade the diagnostic status of 38% of our patients with a suspect of ARVC diagnosis. It should be performed in experienced centers and it should be guided by electro-anatomic mapping, to maximize its diagnostic power.

Funding Acknowledgement

Type of funding source: None
Long-term follow up after renal denervation for the electrical storm management
Authors: Gorev M , Rachkova I.U.I , Gaidukova N.A , Makarycheva O.V , Nardaia S.H.G , Rzaev F.G , Vasilieva E , Shpektor A
Published: November 2020

Background/Introduction

Electrical storm (ES) is a potentially lethal state developing in 4–28% of ICD patients. Neuroaxial modulation (beta-blockers, deep sedation, epidural anesthesia, stellate ganglion blockade etc) is used to decrease arrhythmogenic predisposition of ventricular myocardium to trigger and maintain ventricular arrhythmias. Catheter renal arterial denervation (RDN) is recently described to prevent atrial fibrillation recurrence after pulmonary vein isolation. We used this procedure in addition to standard care to improve the results of ES treatment.

Purpose

This retrospective single-center case-series is aimed to analyze ES patient population and describe the effect of RDN on the in-hospital number of ventricular tachycardia (VT) episodes and ICD shocks and on the mid-term survival.

Methods

Pts admitted to the CCU for more than 3 sustained VT episodes or more than 3 appropriate ICD shocks during the 24h period in 2017–18 were enrolled into study. Demographic, echocardiographic, ICD check up, renal arteries anatomy and mid-term mortality/transplant data were retrospectively analyzed.

Results

Twelve pts (10 male, age 69,3±9,8 years; 2 female, age 72,0±8,5) were included. Nine pts (75%) had CAD, 3 pts (25%) – DCM. Echocardiography revealed LVEF 30±9%, and LV EDV – 216±38 ml. Time from ICD implantation to ES onset was from 4 mos to 13 yrs. In 2 pts RDN was performed after VT ablation, in 1 pt – both RDN and VT ablation were performed during the same procedure, in 4 pts – RDN was done prior to VT ablation and in 5 pts - without VT ablation. Mean number of ablations was 4,8 per artery. The power was 2 to 11 Wt and lesion duration was 90 sec. In 1 pt RF-balloon-based technology was used to achieve RDN. Dramatic decrease in the number of VT episodes (49c52 vs. 6±2) was found in 6/12 pts directly after RDN procedure. In-hospital rhythm control was accessed in 10/12 pts, 1 pt with DCM was transferred for heart transplant despite VT ablation and RDN. There were no RDN procedure related complications in this group of pts. During mean 22 mos of follow-up 2/11 pts needed repeat hospitalization due to ES recurrence (VT ablation and 2-chamber ICD to CRT-D upgrade, respectively, were performed), 2/11 died (1-probably arrhythmic death, 1-other cause), 1/11 was lost for follow up. Total efficacy of RDN after almost 2 years in this study was 50%. Mean LVEF increased to 38±7%.

Conclusion(s)

Catheter renal artery denervation is effective and safe additional procedure to treat ES patients. It allows decreasing the number of ICD shocks and decreases arrhythmogenic potential of ventricular myocardium. Prospective registry is warranted.

Funding Acknowledgement

Type of funding source: None
Causes of recurrences after stereotactic radio-ablation for refractory ventricular tachycardia
Authors: Herrera Siklody C , Jumeau R , Ozsahin M , Moeckli R , Le Bloa M , Porretta A.P , Pascale P , Domenichini G , Haddad C , Bourhis J , Pruvot E
Published: November 2020

Introduction

Stereotactic radio-ablation (STAR) has been recently introduced for the management of ventricular tachycardia (VT) refractory to antiarrhythmic drugs (AADs) and catheter ablation (CA). The incidence and mechanisms of VT recurrences after STAR remain unknown. We report causes of recurrence in patients (pts) after STAR.

Methods

From 09.2017 to 01.2020, 12pts suffering from refractory VT were enrolled. The underlying cardiopathy was ischemic in 3, inflammatory in 3 and idiopathic in 6 pts. Before STAR, an invasive electro-anatomical mapping (Carto3) of the VT substrate (VT-sub) was performed. A mean dose of 22±2Gy was delivered to the VT-sub using the Cyberknife® system.

Results

The ablation volume was 24±7cc and involved the interventricular septum (IVS) in 10. After a median follow-up of 9±7 months, VT burden decreased by 78% (mean value, from 89 to 20 VT/semester). Out of the 12 pts, 9 (75%) presented some form of VT recurrence (table): 1) that spontaneously resolved in 2 pts; 2) remote from the VT-sub in 2 cases; 3) managed with AADs that had failed before STAR in 2 cases; 4) within the treated VT-sub in 3 cases. In the latter 3 cases, one recurrence came from a site adjacent to the circumflex artery (mean dosis 14.4 Gy), and two were located within the treated IVS (one displaying marked fibrosis, and one with sarcoidosis). Only 4/12 (33%) pts required additional CA.

Conclusion

STAR led in our patients to a strong VT burden reduction. Recurrences occurred at sites remote from the irradiated volume, within the IVS or in under-dosed sites adjacent to critical structures.

Funding Acknowledgement

Type of funding source: None
Periodic repolarization dynamics for prediction of mortality: a systematic review and meta-analysis
Authors: Cheng S , Cai M , Liu X , Zhang N , Jin R , Yang S , Hu Y , Hua W , Zhang S
Published: November 2020

Background

Prediction of death is the philosopher's stone of arrhythmology. The electrophysiology has proven to be an important tool to predict the risk of death. Periodic repolarization dynamics (PRD) is a novel electrocardiographic marker that indicates the sympathetic effect on repolarization. PRD qualifies the low-frequency oscillations of cardiac repolarization instability using high-resolution 12 channel 24-h Holter recording. Several studies showed that PRD was an independent predictor of all-cause mortality and cardiac mortality. However, the prediction value of PRD has not been established.

Purpose

To evaluate the prediction value of PRD as an approach of risk stratification that selects patients at a higher risk of death.

Methods

We conducted electronic searches of MEDLINE (PubMed), Embase, Cochrane Register of Controlled Trials (CENTRAL), Science Citation Index Expanded, WHO International Clinical Trials Registry platform (ICTRP) and ClinicalTrials.gov from inception to January 9th, 2020. We also screened for relevant abstracts from conferences including ACC Annual Scientific Sessions, ESC Congress and Annual Congress of the EHRA for the last five years (2014–2019). The primary outcome was all-cause mortality and secondary outcome was cardiac mortality. We included study with large sample size while more than one study were found based on the same originated population. We extracted data from included studies and reported pooled outcomes as hazard ratios (HRs) with 95% confidential intervals (CI) for time-to-event outcomes using DerSimonian-Laird random-effects model. We did statistical analyses using Stata version 12.0 and R version 3.6.1.

Results

5 studies including 6758 patients met all selection criteria for our meta-analysis. Follow-up period ranged from 20.4 to 75.1 months. Among 5 studies, 3 studies considered PRD as dichotomous variable and the cut-off value was 5.75 deg2, while 2 studies considered PRD as continuous variable and coefficient was expressed in standardized units (increase per standard deviation). We did subgroup analysis according to the type of variable because of heterogeneity. There was a significant higher risk of all-cause mortality in PRD ≥5.75 deg2 patients compared with PRD <5.75 deg2 patients (HR 2.37, 95% CI 1.77–3.17). As for continuous variable, increased PRD was a predictor for all-cause death (HR 1.28, 95% CI 1.14–1.42) (Figure). The cardiac mortality was significantly increased in patients with PRD ≥5.75 deg2 vs PRD <5.75 deg2 (HR 3.06, 95% CI 1.66–5.65). Increased PRD was associated with cardiac mortality in continuous variable subgroup (HR 1.34, 95% CI 1.21–1.48) (Figure).

Conclusion

Our findings suggest PRD is a significant predictor of all-cause mortality and cardiac mortality. PRD provides new additional electrophysiological indicator for risk stratification until further investigations are available.

Funding Acknowledgement

Type of funding source: None
Contacts to the healthcare system prior to out-of-hospital cardiac arrests
Authors: Zylyftari N , Moller S.G , Wissenberg M , Folke F , Barcella C.A , Moller A.L , Mills E.H.A , Tan H.L , Kober L , Lippert F , Gislason G.H , Pedersen C.T
Published: November 2020

Background

Patients who suffer a sudden out-of-hospital cardiac arrest (OHCA) may be preceded by warning symptoms and healthcare system contact. Though, is currently difficult early identification of sudden cardiac arrest patients.

Purpose

We aimed to examine contacts with the healthcare system up to two weeks and one year before OHCA.

Methods

OHCA patients were identified from the Danish Cardiac Arrest Registry (2001–2014). The pattern of healthcare contacts (with either general practitioner (GP) or hospital) within the year prior to OHCA of OHCA patients was compared with that of 9 sex- and age-matched controls from the background general population. Additionally, we evaluated characteristics of OHCA patients according to the type of healthcare contact (GP/hospital/both/no-contact) and the including characteristics of contacts, within two weeks prior their OHCA event.

Results

Out of 28,955 OHCA patients (median age of 72 (62–81) years and with 67% male) of presumed cardiac cause, 16,735 (57.8%) contacted the healthcare system (GP and hospital) within two weeks prior to OHCA. From one year before OHCA, the weekly percentages of contacts to GP were relatively constant (26%) until within 2 weeks prior to OHCA where they markedly increased (54%). In comparison, 14% of the general population contacted the GP during the same period (Figure). The weekly percentages of contacts with hospitals gradually increased in OHCA patients from 3.5% to 6.5% within 6 months, peaking at the second week (6.8%), prior to OHCA. In comparison, only 2% of the general population had a hospital contact in that period (Figure). Within 2 weeks of OHCA, patients contacted GP mainly by telephone (71.6%). Hospital diagnoses were heterogenous, where ischemic heart disease (8%) and heart failure (4.5%) were the most frequent.

Conclusions

There is an increase in healthcare contacts prior to “sudden” OHCA and overall, 54% of OHCA-patients had contacted GP within 2 weeks before the event. This could have implications for developing future strategies for early identification of patients prior to their cardiac arrest.

Figure 1. The weekly percentages of contacts to GP (red) and hospital (blue) within one year before OHCA comparing the OHCA cases to the age- and sex-matched control population (N cases = 28,955; N controls = 260,595).

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020
Relationship between episodes of unsustained VTs detected early after an ICD implant and subsequent monomorphic VTs causing appropriate therapy
Authors: Jimenez-Candil J , Perez J , Sanchez M , Hernandez J , Morinigo J.L , Sanchez P.L
Published: November 2020

Introduction

Non-sustained ventricular tachycardias (NSVT) are observed frequently among ICD patients with left ventricular dysfunction (LVD).

Purpose

To analyze the relationship between episodes of NSVTs and monomorphic VTs (MVTs) that subsequently cause appropriate therapies.

Methods

416 ICD patients with LVD (LVEF <45%) followed for 41±27 months. ICD programming (detection and therapies) was standardized. NSVT was defined as any VT of ≥5 beats which did not met the detection criteria occurring within the first 6 months after ICD implant. We analyzed 2201 NSVTs (10+7 beats), which occurred in 250 of the 416 patients (Median=2; IQR=0–7). The mean cycle length (CL) of NSVT was 323±32 ms (adjusted per multiple episodes/patient, generalized estimating equation method (GEEM)).

Results

During the follow-up, 1441 MVT occurred in 183 patients. After showing a significant correlation between burden of NSVT and the occurrence of appropriate therapies due to MVT (C coefficient=0.68; p<0.001), we observed that subjects with >5 NSVT presented an excess of adjusted risk: HR=1.97 (95% CI=1.45–2.72); p<0.001. However, the adjusted mean CL of NSVTs was similar in patients with (322±34) vs. without MVT (324±26 ms); p=0.3.

Among patients who presented NSVTs and MVTs (n=145 subjects), we analyzed the relationship between the adjusted mean CL of the NSVTs (n=1288 episodes) and the CL of the first appropriate therapy due to MVT occurring subsequently. We found a significant and positive correlation between the two (r=0.88; p<0.001); the strongest correlation was observed in subjects with >5 NSVTs (r=0.97, n=52)). The robustness of such correlation was similar in individuals with ischemic (r=0.86; n=91) versus non-ischemic cardiomyopathy (r=0.90; n=54), and in primary (r=0.86; n=75) versus secondary prevention (r=0.90; n=70). The agreement between the CL of first MVT and the adjusted mean CL of NSVT episodes (GEEM) was determined according to the Bland-Altman Method. The difference between the two values was 2±8.3 ms, with only 7.6% (11/145) of patients in whom the difference between the two CL was outside the concordance limits. The agreement was greater, again, in individuals with >5 NSVTs. As shown in the Figure, in more than 95% of patients both values were within the interval of agreement (0.32±4 ms).

Conclusions

1-The burden of NSVTs occurring early after an ICD implant, but not their CL, is associated with a higher incidence of appropriate therapies due to MVT at follow-up.

2-The CL of the NSVTs and that of the first and subsequent MVTs is virtually the same in patients with higher NSVT burden. Therefore, it could be the same tachycardia, but with different duration.

Figure 1

Funding Acknowledgement

Type of funding source: None
Defibrillation threshold modeling to refine implant recommendations for an extravascular ICD system
Authors: Wilkinson J , Blauer J , Abeyratne A , Dhume R , Edmonson J , Haqqani H , Kotschet E , O'Donnell D , Schu C , Severseike L , Swenson D , Takayama J , Crozier I
Published: November 2020

Background

The extravascular ICD (EV ICD) is a novel defibrillator that couples a substernal lead to a device under the left axilla. The electrode locations for best defibrillation performance are unknown. In this study we use data from a 21 patient pilot study to address this question.

Objective

To create computational torso models to study the effect of device and lead position on defibrillation threshold (DFT).

Methods

Finite element models were developed from CT and intraoperative imaging of the 21 patients enrolled in the EV ICD Pilot Study. Between 150 and 200 combinations of electrode locations were created for each patient, including the actual implant locations as determined from post-implant CT. The shock amplitudes from DFT testing and multiple vector impedance measurements from a large subset of patients and their as-implanted models were used to calibrate global model parameters. In total, 3330 implant models were automatically meshed, simulated and analyzed to compute predicted DFT values. For each patient an acceptable implant zone was calculated in which it is predicted that they would pass implant DFT testing. The zones for all patients were aligned and combined using common anatomical landmarks so that a common zone for acceptable DFT performance could be calculated for the cohort.

Results

Two patients were omitted due to incomplete CT data and 16 models were used during the calibration phase. Final analysis was performed using 19 patient models. The model results recommend positioning the lead slightly left of the sternal midline with the most proximal electrode 10 mm above the xiphisternal junction. Similarly, the device should be positioned so that its upper margin is at the height of the leftmost projection of the heart as seen in the AP view, and its posterior margin aligned with the posterior margin of the ventricles. The figure illustrates these positions. The model predicts that using these locations will result in acceptable DFT performance for all 19 patients - including one who failed testing at implant.

Conclusion

Modeling showed that DFT is dependent on both lead and device location. Furthermore, the predicted DFT and impedance values are consistent with clinical measurements. Specific lead and device locations were determined that are both clinically identifiable and provide acceptable DFTs in all patients.

Implant positioning

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Medtronic PLC
Automated screening tool for Subcutaneous Implantable Defibrillator in Brugada syndrome has a high eligibility rate which is predicted by simple electrocardiographic parameters
Authors: Marelli S , Kukavica D , Mazzanti A , Chargeishvili T , Trancuccio A , Monteforte N , Bloise R , Marino M , Napolitano C , Priori S.G
Published: November 2020

Background

Manual electrocardiographic (ECG) screening tools for the use of subcutaneous cardiac defibrillator (S-ICD) have been associated with high ineligibility rates in Brugada syndrome patients (BrS). Although recent works identified ECG parameters for S-ICD eligibility in general population, automated screening tool (AST) for S-ICD eligibility have not even been assessed in large series of patients with BrS.

Purpose

This study evaluates the AST-derived eligibility rates for an S-ICD in patients with BrS, and ECG parameters associated with S-ICD eligibility.

Methods

Screening for S-ICD eligibility was performed using AST in 194 consecutive patients with BrS. Eligibility was defined when at least one of the three vectors was acceptable both in supine and standing position. Twelve-lead ECGs were registered during the screening. ECG parameters associated with AST eligibility were identified using multivariable logistical regression.

Results

Our study population consisted of 194 patients, with male preponderance (n=165/194; 85%); and were 43±12 years old at the time of screening. Majority of patients presented a spontaneous type 1 pattern during screening (n=128/194; 66%), with an average pattern height of 3±3 mm.

Remarkably, 93% of patients passed the screening with AST. No differences in eligibility rates in terms of gender (93% males vs. 93% females eligible; p=1) and age (48±9 years non-eligible vs. 42±12 eligible; p=0.07) existed. Notably, our eligibility rate was 2.5 times higher than rates reported in literature when using manual screening tools (p=0.023). Independent 12-lead ECG parameters (Table) associated with AST eligibility were duration of S wave <80 ms in aVF and R/T ratio ≥3 in lead II (Figure), which have a high positive predictive value (97% and 99%, respectively) for screening eligibility.

Conclusions

Most BrS patients (93%) are eligible for S-ICD when AST is used. S wave <80 ms in aVF, and R/T ratio ≥3 in lead II have a high positive predictive value for S-ICD eligibility.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Italian Ministry of Research and University Dipartimenti di Eccellenza 2018–2022 grant to the Molecular Medicine Department (University of Pavia)
Comparison of de novo and upgrade to resynchronization therapy: a propensity-score matched analysis
Authors: Brandao M , Goncalves Almeida J , Monteiro J , Montenegro Sa F , Fonseca P , Rosas F , Santos E , Ribeiro J , Oliveira M , Goncalves H , Primo J , Braga P
Published: November 2020

Background

Upgrade to resynchronization therapy (CRT) from conventional pacemaker (P) or defibrillator (D) is common practice in Europe. However, guidelines (GL) are discordant: Pacing GL give a class I recommendation, while Heart Failure (HF) GL provide a class IIb indication. Previous studies suggested worse outcomes in upgraded patients (pts).

Aim

To compare response rate and clinical outcomes in a cohort of pts receiving de novo or upgrade to CRT.

Methods

Single-center retrospective study of consecutive pts submitted to CRT implantation (2007–2017). Major adverse cardiac events (MACE) included HF hospitalization (HHF) or all-cause mortality. Clinical response was defined as New York Heart Association class improvement without MACE in the first year of follow-up (FU). Left ventricle end-systolic volume reduction of >15% denoted echocardiographic (echo) response. Survival analysis with Kaplan-Meier method and Log-rank test was performed. Propensity-score matching (PSM) analysis was made to adjust for possible confounder variables.

Results

230 CRT recipients (70.9% male, mean age 67±11 years, 71.5% non-ischemic cardiomyopathy, 39.6% CRT-P) were included, of whom 46 (20%) underwent an upgrade. Upgraded pts were older (69.8 vs 65.9 years, p=0.015), with higher rates of permanent atrial fibrillation (37.0% vs 12.7%, p=0.001), moderate to severe valve disease (45.7% vs 22.3%, p=0.002), chronic kidney disease (37.0% vs 17.2%, p=0.005) and treatment with mineralocorticoid receptor antagonists (79.1% vs 52.0%, p=0.002). They were more likely to receive CRT-P (65.2% vs 33.2%, p<0.001) and CRT-D were more often implanted for secondary prevention (60.0% vs 17.9%, p=0.001). No differences emerged in procedural complications, clinical (74.4% vs 71.4%, p=0.712) or echo (66.7% vs 69.7%, p=0.822) response rates.

During a median FU of 3±4 years, all-cause mortality was similar among groups (Log Rank test, p=0.522, unadjusted hazard ratio [HR] 1.25, confidence interval [CI] 95% 0.62–2.49, p=0.534). There was a statistical tendency for higher MACE rate in the upgrade group (Log Rank test, p=0.064, HR 1.66, CI 95% 0.95–2,91, p=0.076). No differences were found in lead dislodgement (10.9% vs 7.1%, p=0.368) or endocarditis (2.2% vs 4.3%, p=0.692) rates.

PSM analysis identified 88 matched pairs (46 upgrade/42 de novo pts). In this cohort, all-cause mortality (Log Rank test, p=0.77, HR 0.89, CI 95% 0.39–2.03, p=0.78) and MACE (Log Rank test, p=0.36, HR 1.38, CI 95% 0.68–2.81, p=0.37) were comparable between groups [graph no. 1].

Conclusion

Upgrade to CRT was similar to de novo implantation in terms of complications and clinical and echo response, in this cohort. The risk for MACE and mortality was also comparable.

Graph 1

Funding Acknowledgement

Type of funding source: None
10-year outcomes of triple-site versus standard cardiac resynchronization therapy randomized trial (TRUST CRT)
Authors: Mazurek M , Jedrzejczyk-Patej E , Kowalski O , Sredniawa B , Sokal A , Pruszkowska-Skrzep P , Pluta S , Kukulski T , Szulik M , Stabryla-Deska J , Kalarus Z , Lenarczyk R
Published: November 2020

Background

Triple-Site versus Standard Cardiac Resynchronization Therapy Randomized Trial (TRUST CRT) was initiated in 2009 to verify the hypothesis whether triple-site (single right, double left) cardiac resynchronization therapy (CRT) may be superior to conventional, biventricular resynchronization in patients with advanced heart failure.

Objectives

To report 6-month outcomes and 10-year survival in TRUST CRT.

Methods

100 consecutive patients with moderate to severe heart failure, ejection fraction of 35% or less, electrical and mechanical dyssynchrony, were randomly assigned in a 1:1 fashion to triple-site CRT defibrillator (TRIV) or to conventional CRT-D. The primary objective evaluated response-rate, defined as the 6-month's combined end point of alive status, freedom from hospitalization for heart failure or heart transplantation, relative≥10% increase in ejection fraction, ≥10% in peak oxygen consumption, and ≥10% in 6-minute walking distance. The secondary objective was to assess the occurrence of major adverse cardiovascular events (hospitalization for exacerbated heart failure requiring modification of pharmacotherapy, heart transplant or death) at month 6 and during remote observation.

Results

At month 6, the response-rate was higher in triple-site than conventional CRT-D group (51.1 vs. 26.5%, P=0.014). There were 2 deaths or heart failure events in the triple-site group (4%) as compared with 8 in the group assigned to conventional CRT-D (16%). A triple-site resynchronization resulted in 12% absolute risk reduction for secondary end point (hazard ratio 0.25; 95 percent confidence interval, 0.05 to 1.17, P=0.056, in comparison with the conventional CRT-D group). After 10 years of observation (median follow up of 7.1 years; range: 1.2–10.4) 57 patients (58.2%) died: 24 (53.3%) in the triple-site group, 31 (60.8%) in the conventional group (P=0.46) and 2 patients with and ICD (failed CRT implantation) [Figure].

Conclusions

In patients with advanced heart failure, triple-site resynchronization combined with an ICD did not result in better survival than conventional resynchronization therapy in a median observation of 7.1 years.

Figure 1

Funding Acknowledgement

Type of funding source: None
Adequate contacts after remote monitoring alerts were associated with improved outcomes in chronic heart failure: results from the OptiLink HF study
Authors: Wintrich J , Pavlicek V.P , Brachmann J.B , Bosch R.B , Butter C.B , Oswald H.O , Rybak K.R , Mahfoud F.M , Boehm M.B , Ukena C.U
Published: November 2020

Aims

To investigate the effects of adequate reactions to telemedicine alerts triggered by fluid index threshold crossings (FTC) on clinical outcomes in the OptiLink HF trial.

Methods

We separated adequate from inadequate reactions to FTC transmissions in patients with remote impedance-based monitoring (RM) of fluid status in the OptiLink HF trial. Adequate contacts had to meet the following criteria: i) initial telephone contact within 2 working days after FTC transmission, ii) follow-up contacts according to study protocol, and iii) medical intervention initiated after FTC due to true fluid overload. We compared time to cardiovascular (CV) death or heart failure (HF) hospitalization and all CV- and HF-hospitalizations at follow-up between RM patients contacted adequately or inadequately and patients with usual care (UC).

Results

In the RM group, transmission of at least one FTC alert occurred in 356 patients (70.5%; n=505). While 113 patients (31.7%; n=356) have been contacted adequately after every FTC, in 243 patients (68.3%; n=356) at least one FTC was not responded by an adequate contact. Adequate responses to RM significantly reduced risk of the primary endpoint (hazard ratio (HR), 0.68; 95% confidence interval (CI) 0.48–0.95; p=0.025, figure 1), and led to a significantly lower number of CV (52.1±7.5 vs. 99.9±19.8; p=0.007) and HF hospitalizations per 100 patient years when compared with UC (26.1±4.4 vs. 67±15.2; p=0.007).

Conclusion

RM with adequate reactions to FTC alerts significantly reduced total number of both CV and HF hospitalizations and improved clinical outcomes in patients with advanced HF and implantable cardioverter defibrillator (ICD).

Funding Acknowledgement

Type of funding source: None
Incidence and causes of in-hospital mortality in cardiac device-related infections
Authors: Doring M , Ebert M , Lucas J , Hindricks G , Richter S
Published: November 2020

Introduction

Cardiac device-related infections (CDRI) are associated with increased in-hospital mortality despite effective treatment by transvenous lead extraction (TLE) and antibiotic therapy. Data on mortality and causes of death are scarce and predictors of mortality are not well defined.

Purpose

To analyse the incidence and causes of mortality in CDRI and identify predictors of mortality in a large single centre experience.

Methods

All patients undergoing TLE for CDRI in our department between May 2012 and January 2020 were included in a prospective registry. Patient characteristics, procedural and follow-up data were collected and analysed. A Kaplan-Meier analysis was used to analyse the influence of different infection types on mortality. Univariate and multivariate cox regression analysis was applied to identify risk factors for mortality.

Results

Among 561 consecutive patients (72±12 years; 77% male) treated for CDRI (51.2% systemic and 48.8% localized infection), 61 patients (10.9%) died during the index hospitalization. The most frequent cause of death was severe systemic infection or sepsis in 38 patients (6.8%), followed by end-stage heart failure (9; 1.6%), respiratory insufficiency (3; 0.5%), ventricular arrhythmias (3; 0.5%), asystole (2; 0.4%), pulmonary embolism (2; 0.4%), acute enteric ischemia (2; 0.4%), mechanical ileus (1; 0.2%), and unwitnessed sudden death (1; 0.2%). Patients who died had significantly more often systemic infections (p<0.001), positive blood cultures (p<0.001), severe renal dysfunction (GFR <30ml/min; p<0.001), heart failure with reduced ejection fraction (HFrEF; p=0.001), and diabetes (p=0.004). Kaplan-Meier survival analysis showed a significantly higher mortality in patients with systemic CDRI as compared to localized infection (log-rank p<0.001). Several factors were predictors of mortality in univariate analysis: systemic infection (HR 4.64, 95% CI 2.18–9.84; p<0.001), GFR <30 ml/min (HR 4.27, 95% CI 2.57–7.09; p<0.001), vegetation in TOE (HR 3.68, 95% CI 1.78–7.43; p<0.001), positive blood cultures (HR 2.52, 95% CI 1.46–4.37; p=0.001), diabetes (HR 1.89, 95% CI 1.12–3.18; p=0.018), HFrEF (HR 1.83, 95% CI 1.09–3.05; p=0.021), tricuspid regurgitation (HR 1.79, 95% CI 1.21–2.65, p=0.004), and days from hospital admission to explant (HR 1.04, 95% CI 1.02–1.06; p<0.001). Multivariate analysis revealed severe renal dysfunction (HR 2.71, 95% CI 1.47–5.00; p=0.001) and days from hospital admission to TLE (HR 1.029, 95% CI 1.004–1.055, p=0.021) as independent predictors of in-hospital mortality.

Conclusion

In-hospital mortality in CDRI is particularly high in patients with severe systemic infection and sepsis despite state-of the-art treatment. Delayed TLE is associated with an increased in-hospital mortality. Therefore, TLE should be performed early in the course of CDRI, particularly in patients with severe systemic infection.

Funding Acknowledgement

Type of funding source: None
Trends of sex differences in outcomes of cardiac electronic device implantations in the United States
Authors: Mohamed M , Volgman A.S , Contractor T , Sharma P.S , Kwok C.S , Martin G.P , Barker D , Patwala A , Mamas M.A
Published: November 2020

Background

There is limited evidence on the differences in procedural outcomes between sexes after de novo cardiac implantable electronic device implantation (CIED). Furthermore, it is unclear whether any sex-based disparities have changed over the years.

Purpose

To compare procedural outcomes of de novo CIED implantation between sexes and study the trends of these outcomes over a 11-year period in a nationally representative sample.

Methods

Using the National Inpatient Sample, all hospitalisations between 2004 and 2014 for de novo CIED implantation were included, stratified by sex. Multivariable logistic regression was performed to 1) examine the association between sex and in-hospital complications of CIED implantation, expressed as odds ratios (OR) with 95% confidence intervals (CI), and 2) analyse trends of in-hospital outcomes by assessing the interaction term between time (years) and sex as covariates.

Results

Out of 2,815,613 hospitalisations for de novo CIED implantation, 41.9% were performed on women. Women were associated with increased adjusted odds of major adverse cardiovascular events (composite of mortality, thoracic and cardiac complications; OR 1.17 95% CI 1.16, 1.19), procedure-related bleeding (OR 1.13 95% CI 1.12, 1.15), and local complications (thoracic: OR 1.42 95% CI 1.40, 1.44, cardiac: OR 1.44 95% CI 1.38, 1.50). (p<0.001 for all) Notably, there was no difference in odds of all-cause mortality between sexes (OR women: 0.96 95% CI 0.94, 1.00). The odds of adverse complications in the overall CIED cohort were persistently raised in women throughout the study period, whereas similar odds of all-cause mortality across the sexes were observed throughout the study period (see Figure).

Conclusion

In a national cohort of CIED implantations we demonstrate that women are at a persistently higher risk of procedure-related adverse events other than mortality compared to men. This trend is concerning and warrants further work on procedural techniques to neutralise these sex disparities.

Trends of odds of complications in women

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): This work constitutes part of a PhD for MOM that is supported by Medtronic Ltd. Medtronic Ltd. was not involved in the conceptualization, design, conduct, analysis, or interpretation of the current study.
Predictors of major procedure-related complications in transvenous lead extraction
Authors: Doring M , Ebert M , Lucas J , Hindricks G , Richter S
Published: November 2020

Background

Transvenous lead extraction (TLE) has become the mainstay therapy for device-related infections. Though TLE procedures are associated with low complication and high success rates, risk factors for major procedure-related complications remain not well defined.

Purpose

To evaluate the safety and efficacy of TLE in a large single centre cohort and to identify risk factors for major complications.

Methods

All consecutive patients who had undergone TLE in our department between May 2012 and January 2020 were included in a prospective registry. Our protocol for TLE followed a stepwise approach according to lead dwell time and estimated complexity of the procedure: use of simple traction ± locking stylet (LS) ± mechanical and/or powered sheaths ± snare technique. In case of unsuccessful extraction from the venous entry site, femoral or jugular access was approached. Patient characteristics, procedural data and complications were gathered and analysed. Logistic regression analysis was applied to identify risk factors for major procedure-related complications.

Results

A total of 1717 leads (443 [25.9%] ICD leads) were targeted for TLE in 810 patients (67±15 years; 76% male). The mean lead dwell time was 83±60 months. The leading indication for TLE was cardiac device related infection (CDRI) in 527 patients (65.1%), of whom 273 (51.8%) had systemic and 254 (48.2%) localized infection. Two hundred eighty-three patients (34.9%) underwent TLE for non-CDRI causes. Leads were extracted by simple traction in 28.2%, traction with LS in 4.1%, dilator sheaths with LS in 50.1%, and additional use of powered mechanical sheaths in 13.0%. The snare technique was used in 4.6%. Venous access for TLE was exclusively from the entry site in 94.8%, combined from femoral in 4.0% and jugular in 1.2%. TLE was completely successful in 96.2%, partially successful in 2.1%, and failed in 1.7% of all attempted leads, which translated to a clinical success rate of 96.8%.

Eighteen patients (2.2%) experienced minor and 12 patients (1.5%) had major procedure-related complications (cardiac tamponade/perforation) including one intraprocedural death (0.1%) from fulminant pulmonary embolism. Lead-years-per-patient (HR 1.064, 95% CI 1.032–1.096; p<0.001), dwelling time of the oldest lead (HR 1.013, 95% CI 1.007–1.019; p<0.001), and BMI (HR 0.877, 95% CI 0.772–0.997; p=0.020) were significant predictors for major complications in logistic regression analysis.

Conclusion

TLE is feasible, effective and safe in our large single centre experience. Overall complication and failure rates are low. Following our TLE protocol, dwelling time of the extracted leads and low BMI were associated with major procedure-related complications.

Funding Acknowledgement

Type of funding source: None
Impaired high-density lipoprotein function in patients with heart failure
Authors: Emmens J.E , Congzhuo J , Ng L.L , Voors A.A , De Boer R.A , Tietge U.J.F
Published: November 2020

Background

We recently showed that a lower high-density lipoprotein cholesterol (HDL-C) concentration was one of the strongest predictors of death or heart failure (HF) hospitalisation in patients with HF. In a follow-up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to prognosis of HF patients has not been addressed.

Methods

We measured three key HDL function metrics, namely cholesterol efflux, antioxidative capacity, and anti-inflammatory capacity, at baseline and after 9 months in 446 randomly selected HF patients from BIOSTAT-CHF. Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients.

Results

From baseline to 9 months, HDL-C concentrations did not substantially change, but HDL-mediated cholesterol efflux and anti-inflammatory capacity had decreased (both P<0.001). In contrast, antioxidative capacity improved during the 9 months follow-up (P<0.001). Higher HDL-mediated cholesterol efflux was independently associated with lower risk of mortality after adjustment for BIOSTAT risk models and log HDL-C (HR=0.81 [95% CI: 0.71–0.92], P=0.001). Other functionality parameters were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux, and apolipoprotein A1 emerged as the main protein associated with all three functionality parameters.

Conclusions

HDL-mediated cholesterol efflux and anti-inflammatory capacity significantly decreased over time in patients with HF. Better baseline cholesterol efflux was prospectively associated with reduced mortality during follow-up independent of HDL-C. Combined these data indicate that HDL function measurements have the potential to provide clinical information beyond static HDL-C concentrations in HF patients.

Changes in HDL functionality over time

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Commission
Global differences in heart failure with preserved ejection fraction: the paragon-hf trial
Authors: Tromp J , Clagget B.L , Jhund P , Kober L , Widimsky J , Chopra V , Ge J , Maggioni A.P , Martinez F , Zannad F , Lefkowitz M.P , Shi V.C , McMurray J.J.V , Solomon S.D , Lam C.S.P
Published: November 2020

Background

Heart failure with preserved ejection fraction (HFpEF) is a global public health problem with important regional differences. We investigated these differences in the PARAGON-HF trial, the largest, most inclusive global HFpEF trial.

Methods

We studied differences in clinical characteristics, outcomes and regional treatment effects of Sacubitril/Valsartan in 4796 patients with HFpEF from the PARAGON-HF trial, grouped according to geographic region.

Results

Regional differences in patient characteristics and comorbidities were observed (Figure 1): patients from Western Europe were oldest (75±7 years) with the highest prevalence of atrial fibrillation (36%); Central/Eastern European patients were youngest (71±8 years) with the highest prevalence of coronary artery disease (CAD, 49%); North American patients had the highest prevalence of obesity (64%) with metabolic syndrome; Latin American patients were youngest and had a high prevalence of obesity (53%); Asia-Pacific patients had a high prevalence of diabetes (44%) despite low prevalence of obesity (26%). Rates of the primary composite endpoint of total hospitalizations for HF and death from cardiovascular causes was lowest in patients from Central Europe (9 per 100 patient years) and highest in patients from North America (28 per 100 patient years), which was primarily driven by a greater number of total hospitalizations for HF and independent of confounders. In the total population, sacubitril–valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes with no significant heterogeneity in treatment response to sacubitril-valsartan across regions.

Conclusion

This first report on regional differences in the largest prospective global trial in HFpEF suggests substantial regional heterogeneity with respect to phenotype, outcomes and quality of life.

Figure 1

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Study funded by Novartis
Global constructive work and left atrial reservoir function is reduced in patients with heart failure with preserved ejection fraction compared with patients with preclinical diastolic dysfunction
Authors: Tunyan L.G , Chilingaryan A.L , Adamyan K.G , Zelveyan P.H , Tumasyan L.R , Kzhdryan H.K
Published: November 2020

Heart failure with preserved ejection fraction (HFpEF) remains an unresolved issue with morbidity and mortality comparable with that of reduced EF HF. Diastolic dysfunction (DD) is the hallmark of HFpEF but it is unclear why some patients do not develop symptoms and remain in preclinical DD (PDD) stage with the same degree of DD as patients with HFpEF. We assumed that patients with HFpEF might have more deteriorated global myocardial work (GW) and left atrial reservoir longitudinal strain (LALS) parameters compared with PDD patients.

Methods

210 patients (150 female, mean age 71±5 years) of which 118 with PDD and 92 with HFpEF were enrolled in this study. PDD was diagnosed if patients had normal NT-proBNP values, and at least 3 of the following echocardiographic criteria at rest or after diastolic stress echocardiography: end-systolic left atrial volume index (LAVi) >34 ml/m2, LV E/e' >13, average LV e' >8.5, and systolic pulmonary artery pressure >30 mmHg. GW index (GWI) was obtained from pressure-strain loops composed from speckle tracking analysis indexed to brachial systolic blood pressure, global constructive work (GCW) was measured as the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation, global wasted work (GWW) was calculated as energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation, and GW efficiency (GWE) as the percentage ratio of constructive work to the sum of constructive work and wasted work. LALS was measured by speckle tracking echocardiography as average value of two basal segments in apical 4 chamber view along LAVi and 4D LV mass index (LVMi) offline by experienced echocardiographer who was unaware of the study aims.

Results

Patients with PDD and HFpEF have comparable values of LAVi, LVMi, GWI, GWW, and GWE (LAVi 38.4±3.9 ml/m2 vs 39.1±4.1 ml/m2, p=NS; LVMi 82.8±11.4 g/m2 vs 83.5±10.2 g/m2, p=NS; PDD GWI 2389±154 mmHg% vs 2368±139 mmHg%, p=NS; GWW 62±5 mmHg% vs 65±4 mmHg%, p=NS; GWE PDD 89±9% vs 87±11%, p=NS). LALS and GCW were significantly reduced in patients with HFpEF compared with PDD patients (LALS 21.3±7% vs 29±5%, p<0.01; GCW 1964±112 mmHg% vs 2259±164 mmHg%, p<0.01).

Conclusion

Patients with HFpEF have reduced LALS and GCW compared with PDD patients. Both parameters are indicative for LA and LV myocardial fibrotic burden respectively which might be one of the probable explanations of PDD transition to HFpEF.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Committee of Science at Ministry of Education of Republic of Armenia