bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipomatous metaplasia is the best CT predictor for conducting channel localization in scar-related ventricular tachycardia ablation
Authors: Zucchelli G , Parollo M , Mazzocchetti L , Segreti L , Barletta V , De Lucia R , Grifoni G , Sbragi S , Canu A , Viani S , Paperini L , Soldati E , Di Cori A
Published: November 2023

Introduction

Recent evidence has shown that intramyocardial lipomatous metaplasia (LM) can be directly identified with cardiac computer tomography (CT) and plays a significant role in ventricular arrhythmogenesis and facilitation in structural heart disease.

Purpose

We sought to explore the diagnostic performance of three different CT features (LM, CT channels, wall thinning) identified at ADAS3D post-processing as electroanatomical substrate predictors and their potential role in planning and aiding ventricular tachycardia (VT) scar dechanneling procedures.

Methods

All patients undergoing VT ablation at our institution were enrolled. CT images were post-processed with ADAS3D software to assess LM and left ventricle wall thickness. Images were then retrospectively imported into CARTO3 software and concordance between CT and electroanatomical features (conducting channels, channel entrances, bipolar scar, voltage channels, ablation VISITAGs) was assessed at a cardiac segment level.

Results

From July 2016 to December 2022 131 patients underwent VT ablation at our institution. 88 patients did not undergo preprocedural CT examination, 15 patients had a low-quality CT scan and, at ADAS3D analysis 9 patients did not have significant LM. 19 patients (14 ischemic and 5 non-ischemic, 323 cardiac segments) were then included for analysis. 90 segments (27,86%) showed LM, 93 segments (28,79%) showed thickness < 5 mm and 12 segments (3,72%) held CT channels. In terms of conducting channel prediction, in ischemic patients, LM showed 70% sensitivity, 89% specificity, 73% PPV and 88% NPV when compared to CT channels (10% sensitivity, 98% specificity, 70% PPV, 72% NPV) or wall thinning (61% sensitivity, 82% specificity, 58% PPV and 84% NPV). In non-ischemic patients LM showed with 69% sensitivity, 81% specificity, 39% PPV and 94% NPV when compared to CT channels (15% sensitivity, 100% specificity, 100% PPV, 87% NPV) or wall thinning (46% sensitivity, 82% specificity, 32% PPV and 89% NPV). Overall, at multivariate analysis only LM (OR 12,46 95% C.I. 6,59-23,58) and wall thinning (OR 4,73 95% C.I. 2,45-9,14) were independent predictors for conducting channel.

Conclusion

Lipomatous metaplasia is the best CT predictor for conducting channel presence both in ischemic and non-ischemic patients with scar related ventricular tachycardia and a potentially useful tool for procedure planning and guidance.CT predictors for EAM substrate findingsMultivariate forest plots
A valuable electrophysiological insight to distinguish right from left outflow tract ventricular arrhythmia -local activation time in the anterior intraventricular vein and distal great cardiac vein-
Authors: Doi J , Hachiya H
Published: November 2023

Background

Although several ECG criteria have been helpful to differentiate right from left outflow tract ventricular arrhythmias (OTVAs), discriminating OTVA origins especially with left bundle branch block (LBBB) is still considered challenging.

Objective

The aim of this study was to investigate the local activation time (LAT) in the anterior intraventricular vein (AIV) and distal great cardiac vein (d-GCV), and to identify an electrophysiological method of distinguishing right from left OTVAs.

Methods

We measured the LAT relative to the QRS onset of OTVAs in the AIV and d-GCV using a microelectrode with a lumen catheter in patients undergoing successful OT-VA ablation between January 2017 and July 2022 in our institution. The ECG parameters such as the V2 transition-ratio and V2S/V3R index to distinguish right-OT-VAs from left-OT-VAs with LBBB were also investigated.

Results

Local potentials at the AIV and/or d-GCV OTVA sites in 76 consecutive patients (mean age: 56.5±16.2 year-old, right-OTVAs:40, left-OTVAs:36) were analyzed. The LAT of the AIV/d-GCV was significantly shorter for right-OTVAs than left-OTVAs (d-GCV -26.7±26.8 vs. -2.7±21.4 msec, p<0.001, AIV -9.9±23.2 vs. 16.9±18.2 msec, p<0.001), and associated with the identification of right-OTVAs and left-OTVAs (AUC: d-GCV: 0.76 [95%CI 0.65-0.86], AIV: 0.81 [0.70-0.92]). Defining a LAT <0ms in the AIV (sensitivity: 0.74, specificity: 0.75), <-24ms in the d-GCV (sensitivity: 0.83, specificity: 0.60) as cutoff values respectively, the overall odds ratio (OR) increased more for right-OTVAs than left-OTVAs (OR; AIV: 6.7 [1.9-23.4], p=0.002, d-GCV: 7.5 [2.5-22.1], p<0.001). In the multivariate analysis, a LAT<-24ms in the d-GCV was revealed as an independent predictor certifying right-OTVA origins (OR 14.4 (2.1-95.1), p=0.006), which was superior to the V2 transition-ratio and V2S/V3R index.

Conclusion

The AIV/d-GCV activation time could outperform other previous ECG criteria to discriminate right-sided from left-OTVA ventricular arrhythmias with LBBB.
Left ventricular afterload reduction by transcatheter aortic valve implantation acutely alleviates right ventricular pacing-induced left ventricular dysfunction in patients with aortic stenosis
Authors: Ruppert M , Lakatos B K , Osztheimer I , Molnar L , Zima E , Geller L , Kosztin A , Straub E , Papp R , Tarjanyi Z , Ladanyi Z S , Turschl T , Kovacs A , Merkely B
Published: November 2023

Introduction

In patients with left bundle branch block (LBBB) cardiac function has been found to be particularly sensitive to alterations in left ventricular (LV) afterload. Nevertheless, whether the detrimental hemodynamic effect of right ventricular pacing (RVP)-induced electromechanical dyssynchrony on LV function is also associated with afterload dependency, has not been investigated yet.

Purpose

Hence, in the current study we sought to examine the acute effect of RVP on LV function in patients with aortic stenosis (AS) before (with elevated afterload) and after (without elevated afterload) transcatheter aortic valve implantation (TAVI).

Methods

Patients with a previously implanted permanent pacemaker (PM) and significant AS referred for TAVI at our heart and vascular center university were screened for this observational study. Only those patients who had an intrinsic, regular, narrow QRS or right bundle branch block (RBBB) morphology rhythm were included. From 2022 March to 2023 February, nine patients with a DDD PM (with sick sinus syndrome and maintained AV conduction) and four patients with a VVI PM (with atrial fibrillation and complete AV block but stable junctional escape rhythm) were enrolled. Following TAVI, four patients were excluded due to the development of new-onset persistent LBBB. Transthoracic conventional and advanced echocardiography and non-invasive blood pressure monitoring were performed immediately before TAVI and on the second postoperative day. The measurements were carried out during intrinsic QRS rhythm and during frequency-matched RVP as well. Global longitudinal strain was determined by speckle-tracking echocardiography, then using LV pressure curves estimated from systolic blood pressure and mean aortic gradient, global myocardial work index (GMWI) was calculated to assess LV contractility.

Results

Mean aortic gradient was decreased after TAVI (40.2±3.6 vs. 6.7±1.3mmHg before vs. after TAVI, P<0.001) indicating successful reduction of LV afterload. Compared to the intrinsic QRS rhythm, RVP decreased GMWI before TAVI (GMWI: 1967±206 vs. 1240±174mmHg% intrinsic QRS vs. RVP, P<0.001) and after TAVI (GMWI: 1399±149 vs. 1020±121mmHg% intrinsic QRS vs. RVP, P=0.019) as well. Nevertheless, the extent of RVP-induced LV contractility impairment (expressed as ΔGMWI) was significantly alleviated after pressure unloading therapy (ΔGMWI: -37.1±6.6 vs. -24.5±7.8% before TAVI vs. after TAVI, P=0.024).

Conclusion

Our preliminary results indicate that RVP-induced LV dysfunction is afterload dependent. Hence, in patients with AS and a high percentage of RVP, TAVI might entail substantial functional improvement.
Impact of clinical frailty on the outcome of pacing for bradyarrhythmias in a district general hospital population
Authors: Warraich M , Haggag A , Ayyaz A , Sunni N
Published: November 2023

Background and Aims

There is good evidence for mortality with increasing age, heart disease, peripheral vascular disease, pulmonary disease and renal disease in implantable cardiac defibrillators. And while multimorbid states and fragility are considered in decision to offer for more complex cardiac electronic device implants1,2 we aimed to characterise how much frailty and co-morbidities impact mortality in patients receiving simple bradyarrhythmia cardiac pacing device implants.

Methods

Retrospective examination of 700 consecutive novel standard bradyarrhythmia cardiac device implants (DDD, VVI, AAI) at Walsall Manor Hospital between 01/01/2016 to 28/02/2021 was undertaken through the electronic patient record. Patients’ frailty was calculated with Rockwood Frailty Score (RFS) and comorbidities at the time of implant recorded.3 Prospective follow up until 14/02/2023 was conducted, allowing at least a 2 year follow-up for all surviving patients. Results were analysed with Kaplan-Meier survival curves and Hazard Ratios (HR) and Risk Ratios (RR).

Results

Mean age of implant was 78.4±10.3 with mortality rate of 87/700 (12.4%) at one year and total 282/700 (40.3%). Overall, a RFS of 5 or more was associated with death overall HR 2.05 (95% CI 1.61-2.60) and 3.42 (95% CI 2.23-5.24) within 1 year (Fig. 1).

Heart failure (OR 2.38, 95% CI 1.59-3.57), valvular heart disease (OR 3.19, 95% CI 2.08-4.89), atrial fibrillation/flutter (OR 1.44, 95% CI 1.09-1.91), chronic kidney disease (OR 1.89, 95% CI 1.296-1.72), malignancy (OR 1.91, 95% CI 1.08-3.36) were important co-morbidities of death within one year of implant. Ischemic heart disease and cognitive impairment including dementia demonstrated a trend towards worse mortality but did not reach significance (Fig. 2).

Conclusion

High frailty score as well as comorbidities including heart failure, valvular heart disease, atrial fibrillation, chronic kidney disease and malignancy indicate increased risk of early death after novel implant of bradycardia cardiac pacing device implants. Although advanced age alone is not a barrier to offer pacing, consideration should be given to advanced frailty and multimorbid states which may detract from any perceived benefit bradyarrhythmia correction may offer. These data have impacted our shared decision making during the consent process with our patients and in our multidisciplinary team discussions.Figure 1Figure 2
Development and validation of a nomogram predicting all-cause mortality for patients with an implantable cardioverter-defibrillator
Authors: Zhou B , Sun X , Zhao S , Chen K , Hua W , Su Y , Yang J , Liang Z , Xu W , Tang M , Yan H , Zhang S
Published: November 2023

Background

For patients with high risk of sudden cardiac death, despite the benefits of an implantable cardioverter defibrillator (ICD), some patients are still at a high risk of death. Death risk assessment of ICD patients is beneficial to the clinical management of such patients.

Purpose

The purpose of this study was to develop and validate a nomogram predicting all-cause mortality for patients with an ICD.

Methods

We retrospectively analyzed the data of multicenter ICD registration study (SUMMIT study) from 2010 to 2014 in China. A total of 617 ICD patients from regions where the enrollment ranked top five formed a development cohort. The physical activity monitored by ICD and clinical data were collected. Univariate and multivariate COX regression analyses were used to screen mortality predictors and construct the nomogram. The performance of nomogram was evaluated by the C index and the calibration curve. A total of 196 ICD patients from other regions formed a validation cohort, and the nomogram constructed by the development cohort was further evaluated in the verification cohort.

Results

In the development cohort, physical activity, diabetes and left ventricular end-diastolic diameter were selected as mortality predictors by univariate and multivariate proportional hazard model analysis. The nomogram was constructed by these three factors. The C index of the nomogram was 0.80 (95% confidence interval, 0.75-0.84). The calibration curve showed that the predicted survival probability of the nomogram was in good agreement with the actual survival probability. In the validation cohort, the C index of the nomogram was 0.74 (95% confidence interval, 0.64-0.84), and the calibration curve still maintained good consistency.

Conclusion

Our study develops and validates a nomogram predicting all-cause mortality for patients with an ICD by integrating the physical activity monitored by ICD and clinical data. The nomogram performs well and can provide personalized death risk assessment for ICD patients.Figure 1Figure 2
Chronic safety and performance of the extravascular ICD: results from the global EV ICD Pivotal study
Authors: Boersma L , Friedman P , Murgatroyd F , Manlucu J , Knight B P , Clementy N , Leclercq C , Amin A , Merkely B P , Birgersdotter-Green U M , Chan J Y S , Biffi M , Knops R E , Wiggenhorn C , Crozier I
Published: November 2023

Background

Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death in patients at high risk for ventricular arrhythmias, but conventional systems carry a risk of transvenous (TV) lead-related complications. The novel extravascular ICD (EV ICD) may reduce some of these complications, while offering anti-tachycardia pacing (ATP), pause prevention pacing, and a device of similar size and projected battery longevity as a TV ICD, by placing a lead substernally. The EV ICD Pivotal study demonstrated EV ICD safety and performance for termination of ventricular arrythmias at 6 months. Longer-term performance is unknown.

Purpose

To report the chronic safety and performance of the EV ICD system.

Methods

The extravascular implantable cardioverter defibrillator (EV ICD) Pivotal study was a prospective, international, single-arm, premarket clinical study. Patients with a class I or IIa indication for a single-chamber ICD per ESC or ACC/AHA/HRS guidelines were enrolled. Freedom from major system- and/or procedure-related complications at 18 mo was evaluated, as well as conversion of arrhythmias by anti-tachycardia pacing (ATP) or shock through all available follow up. Rates of ATP success were evaluated using the generalized estimating equation (GEE) and simple proportions.

Results

Implantation was attempted in 316 patients: 74.7% male, age 53.8±13.1 years, 82% primary prevention, left ventricular ejection fraction of 38.9%±15.4%, and New York Heart Association Class I (23.4%) or II/III (65.5%).

Of 299 implanted patients (average follow up 16.2±7.2 mo), 19 experienced 80 spontaneous, appropriately treated arrhythmic episodes: 37 treated by ATP, 15 by ATP and shock, and 28 by shock alone with a Kaplan-Meier (KM) estimated 6.8% of patients experiencing appropriate therapy by 18 mo (Figure). Of discrete episodes treated with shock, 21/21 (100%) were successfully terminated. ATP was delivered in 12 patients, successfully treating 35/52 episodes (67.3%; GEE adjusted 59.0%). Inappropriate shocks occurred in 35 patients through all follow up, with a rate of 10.2% at 1 year.

The KM estimate of freedom from major EV ICD system-or procedure-related complications rate through 18 mo was 91.9% (95% CI: 88.2% to 94.4%). The most common event was lead dislodgment (10 events in 9 patients) identified 0 to 120 days post-implant, predominantly due to anchoring technique.

Conclusion

The safety and effectiveness of a novel EV ICD system with a substernal lead extends through chronic follow up. Shocks were avoided in nearly half of all spontaneous episodes because of the availability of ATP.Figure
Marked differences in ICD therapy frequencies between phenotypes
Authors: Zheng C , Christensen A H , Joens C , Risum N , Bosselmann H S , Philbert B T , Frosted R , Bundgaard H
Published: November 2023

Background

Implantable cardioverter defibrillators (ICD) are implanted due to a broad range of cardiac conditions according to guidelines.

Purpose

The aim of this study was to compare the distribution of ICD therapies across different cardiac diseases.

Methods

In this descriptive study, we included patients from Eastern Denmark with an ICD implanted up until November 2021. Data was obtained from the national ICD registry and the diagnosis leading to implantation of the ICD was registered. ICD interrogations and number of episodes of appropriate ICD therapies (shock/anti-tachycardia pacing (ATP)) were obtained. End of follow-up was November 8, 2021 or date of death or heart transplantation. Cumulated numbers of therapies were calculated for each patient during the follow-up period (shock/ATP therapies per 1,000 patients per year).

Results

Data on 3,068 patients (median (IQR) age at implantation 65 years (56-72)) across 10 cardiac disorders was obtained (Figure). A total of 1,403 patients had the ICD implanted as primary prophylaxis and 1,554 as secondary prophylaxis and in 111 patients it was unclear. Mean follow-up time of 595 years per diagnostic subgroup (210-12,911 years). The median (IQR) shock/ATP rate per 1,000 patients per year was 1.47 (0.70-2.62). The numerically highest shock/ATP rate of 28.9 therapies per 1,000 patients per year was seen in patients with arrhythmogenic right ventricle cardiomyopathy and the lowest shock/ATP rate of 0.05 therapies per 1,000 patients per year was seen in patients with ischemic heart disease. In patients with ischemic heart disease, the shock/ATP rate per year was 0.06 in patients with an ICD implanted as primary prophylactic and 0.15 in patients with an ICD as secondary prophylactic.

Conclusion

The frequency of ICD shock/ATP therapy varies several-fold between cardiac disorders, with the highest rate in patient with arrhythmogenic right ventricle cardiomyopathy and the lowest rate in the major group of patients, i.e. patients with ischemic heart disease. These findings may indicate a need for adjustments of patient selection for ICD implantation.
Left ventricular anterolateral site is the preferable left ventricular lead position for an upgrade to biventricular pacing
Authors: Ogano M , Iwasaki Y , Okada T , Tanabe J , Shimizu W , Asai K
Published: November 2023

Background

Cardiac resynchronization therapy (CRT) is a well-established treatment for symptomatic heart failure with electrical dyssynchrony. The LV lead position in patients with left bundle branch block is usually recommended at the LV posterolateral to the lateral site, which is the latest electrical activation site. In contrast, the preferable LV lead position in patients who plan to upgrade from conventional RV apical pacing to CRT remains unclear.

Purpose

This study aimed to identify the preferable LV lead position for upgrading to CRT from conventional RV apical pacing.

Methods

An electrophysiological study was performed on patients who underwent ablation for atrial fibrillation. The electrode catheters were positioned at the RV apex, LV anterolateral, and LV posterolateral sites via the coronary sinus branches. During RV apical pacing, the activation time from the RV apex to the LV anterolateral and posterolateral sites was measured, and the activation time ratio to QRS duration was calculated. Biventricular pacing from both the RV apex and LV anterolateral or LV posterolateral sites was performed, and the difference in QRS duration and LV dP/dt compared to only the RV apical pacing state was measured.

Results

We enrolled 37 patients who exhibited anterolateral and posterolateral LV coronary sinus branches. During RV apical pacing, the average activation time ratio to QRS duration was higher at the LV anterolateral site than at the LV posterolateral site (0.89±0.07 vs. 0.71±0.11, P <0.001). The shortening ratio of QRS duration during biventricular pacing compared to baseline RV apical pacing was greater at LV anterolateral site than at the LV posterolateral site (45.7±18.0% vs. 32.0±17.6%, P <0.001). The improvement ratio of LV dP/dt during biventricular pacing was also better from the LV anterolateral site than from the LV posterolateral site (12.7±8.9% vs. 3.7±8.2%, P <0.001).

Conclusion

LV lead position in patients who plan to upgrade to CRT from conventional RV apical pacing is preferably at the LV anterolateral site.
Biventricular or conduction system pacing for cardiac resynchronization therapy: a proposed treatment algorithm based on interventricular conduction delays
Authors: Landra F , Marallo C , Taddeucci S , Sisti N , Pica A , Stefanini A , Tavera M C , Pagliaro A , Baiocchi C , Santoro A
Published: November 2023

Background

Cardiac resynchronization therapy (CRT) is usually performed with biventricular pacing (BiVP), but recently conduction system pacing (CSP) has been proposed as an alternative in case of unsuccessful coronary sinus lead implantation. However , further evidence is needed to determine when CSP should be used in lieu of BiVP to improve clinical benefit.

Purpose

To assess the clinical benefit of a treatment algorithm based on interventricular conduction delays (IVCD) to choose between BiVP or CSP in candidates to CRT.

Methods

Consecutive patients presenting at our Institution from January 2018 to December 2020 with an indication to CRT were prospectively enrolled in the study group (delays-guided resynchronization group, DRG). IVCD were measured after left ventricle (LV) lead positioning in a lateral or posterior-lateral cardiac vein, when feasible, using endocavitary electrogram. Treatment algorithm based on IVCD was used to decide whether to leave LV lead to perform BiVP or pull it out and perform CSP. An historical cohort of patients who underwent CRT from January 2016 to December 2017 independently from IVCD was used as a control group (standard resynchronization group, SRG). The primary endpoint was a composite of cardiovascular mortality, heart failure (HF) hospitalization, or urgent unplanned clinic visits at 1 year after the date of intervention.

Results

Study population consisted in 292 patients, of which 160 (54.8%) in the DRG and 132 (45.2%) in the SRG. Age, sex, HF etiology, NYHA class, left ventricular ejection fraction and QRS duration and morphology did not differ between the two groups. In the DRG 41 of 160 patients underwent CSP based on treatment algorithm (25.6%). The primary endpoint was significantly reduced in the DRG (35/160, 21.8%) compared to SRG (48/132, 36.4%)(hazard ratio (HR): 1.72; 95% confidence interval (CI):1.12-2.65; p=0.013).

Conclusion

A treatment algorithm based on IVCD shifted 1 patient every 4 from BiVP to CSP, with consequent reduction in cardiovascular deaths, HF hospitalizations or urgent unplanned clinic visits after implantation. Therefore, its application could be useful to determine whether to perform BiVP or CSP in CRT candidates.Treatment Algorithm
Contemporary management and awareness of cardiac implantable electronic device infection: a European survey
Authors: Weil J , Atar D , Rao A
Published: November 2023

Background

Cardiac Implantable Electronic Device (CIED) infections pose a significant risk to patient health and can be life-threatening. Despite this, there exist significant disparities in knowledge and a lack of adherence to established guidelines regarding their management and prevention.

Purpose

In order to gather valuable insights into overall awareness of CIED infections and the current practice patterns in Europe, we conducted a survey aimed at evaluating the knowledge and skills of healthcare practitioners and identifying areas that require improvement.

Methods

A double-blinded online survey was conducted among General Cardiologists (GCs) and Electrophysiologists (EPs) in Europe who were not skilled in lead extraction, and in full-time, active practice between April and May, 2022. The survey collected key demographic data and used multiple-choice questions as well as two clinical vignettes to assess the skills and knowledge.

Results

In total, 240 physicians (120 EPs and 120 GCs) from four European countries (Germany, UK, Italy, and France) responded to the survey. About 83% of the physicians were affilicated with public hospitals. On average, EPs had 16 years and GCs had 17 years in practice, with experience managing 305 and 233 CIED patients, respectively. The majority of the respondents (87% EPs, 84% GCs) would replace the full device in the case of a system infection. However, when dealing with pocket infection with negative blood culture and no fever, only about 36% of EPs and 20% GCs would recommend complete system replacement, with GCs more likely to only replace the device without lead removal. Most EPs (92%) were familiar with EHRA/HRS guidelines for CIED lead management and extraction. Significantly more EPs in Germany (27%) were unfamiliar compared to EPs from other three countries (0%, 0% and 3% for UK, Italy and France, respectively). Overall, less GCs (89%) were familiar with guidelines, with significantly more UK GCs (27%) unfamiliar compared to GCs from Italy (7%) and France (0%). Majority of physicians (83% EPs and 82% GCs) believe that Class I indications for lead management are frequently adhered to in their facility, with more physicians in France (40%) believing that their facility always adheres as compared to those in other countries (7%, 7%, and 17% for Germany, UK and Italy, respectively).

Conclusions

Although there is a high familarty with guidelines for CIED lead management and extraction, gaps in adherence to infection management recommendations in practice still exist. There is a need of education to increase guideline awareness and understanding of the severity of pocket infection, especially among GCs and physicians in certain countries.
Cassandra speaks: a case series of unanticipated subcutaneous ICD premature battery depletion in a single-centre experience
Authors: Lazzeri M , Carecci A , Bertelli M , Quaranta A , Spadotto A , Bartoli L , Massaro G , Angeletti A , Frisoni J , Valzania C , Diemberger I , Martignani C , Ziacchi M , Galie' N , Biffi M
Published: November 2023

Background

Subcutaneous ICDs (S-ICD) are a valuable option in sudden cardiac death prevention. The main advantage over conventional transvenous ICDs is the absence of intravascular hardware for patients without the need for cardiac stimulation, resynchronization therapy or anti-tachycardia pacing. The claim of reduced lead-related complications has on the contrary been challenged by recent warnings of unexpected lead fracture. Moreover, concerns related to premature battery depletion (PBD) leading to unanticipated device replacement are increasing.

Purpose

To evaluate retrospectively the incidence of unanticipated S-ICD premature battery depletion in a single-centre experience.

Method

168 consecutive patients implanted with S-ICD from February 2015 to November 2022 in our tertiary cardiology centre were included in this study. 4 patients moved to other sites and were thus lost to follow-up, leaving a total of 164 patients. PBD was defined as the occurrence of battery depletion requiring generator replacement earlier than 60 months post-implantation in the absence of therapy being delivered, or as a result of manufacturer recommendations.

Results

Most patients were implanted for primary prevention (101 patients, 60%). The main aetiology was hypertrophic cardiomyopathy (47 patients, 28%), followed by arrhythmogenic (35, 21%) and dilated idiopathic cardiomyopathy (24, 14%). Mean age and left ventricular ejection fraction at baseline were 46±18yrs and 51±16%, respectively.

Over a total follow up period of 44±25 months, at 58±17 months following implantation 19 (11,6%) patients needed early replacement due to PBD, while 2 (1.2%) patients had lead fracture after respectively 41 and 26 months, for a total of 12,8% of patients with system-related complications. In addition to those patients requiring early replacement due to PBD or lead fracture, two underwent S-ICD extraction due to infection. Analysis of freedom from unanticipated PBD per year of implantation showed higher rates in years 2016 and 2017, with 67% and 27% of all implanted patients, respectively (Figure 1).

Conclusions

In this study, the incidence of PBDs appear to be higher than reported in literature though confined to a limited device series. However, if on the contrary the trend should remain remarkably high, that would not only endanger patients health due to repeated replacements, but also pose a huge economic burden to health systems.
Interleukin 17A-correlated myocarditis in patients with psoriasis: cardiac recovery following secukinumab administration
Authors: Frustaci A , Galea N , Dominici L , Verardo R , Alfarano M , Scialla R , Richetta A G
Published: November 2023

Background

Psoriasis (PS) is a common immune-mediated disease of the skin with possible extension to joints, aorta and eye. Myocardial inflammation has been rarely suggested.

Purpose

Report of PS-related myocarditis.

Methods

One hundred consecutive patients with PS were screened for cardiac involvement. Among them, five male patients (aged 56 ± 9.5 years) with moderate-severe form showed a dilated cardiomyopathy (LVEF <35%) with normal coronary arteries and valves. They underwent a left ventricular endomyocardial biopsy for evaluation of myocardial substrate. Endomyocardial samples were processed for histology and immunohistochemistry, including myocardial expression of Toll-Like Receptor 4 (TLR4) and interleukin-17A (IL-17A), which plays a major role in psoriasis pathogenesis; real-time PCR for cardiotropic viruses and Western blot analysis for myocardial expression of IL-17A. Patients’ sera were tested for anti-heart autoantibodies.

Results

An active lymphocytic myocarditis was revealed in all 5 patients, characterized by absence of viral genomes at PCR, positive anti-heart autoantibodies, overexpression of TLR-4 and enhancement of IL-17-A at western blot analysis showing a 2,48-fold increase in psoriatic myocarditis compared with no psoriatic myocarditis and a 6-fold increase compared to myocardial controls. Treatment included combination of prednisone (1 mg/Kg daily for 4 weeks, tapered to 0.33 mg/Kg) + azathioprine (2 mg/Kg, daily) in 3 pts or secukinumab (SK, 100 mg/monthly) in 2 pts for 6 months. LVEDD and LVEF improved in the first 3 pts (-14% and + 118%, respectively) while completely recovered (LVEF> 50%) in the last 2 pts on SK.

Conclusion

IL-17A-related myocarditis can occur in up-to 5% of patients with psoriasis. It manifests as a progressive dilated cardiomyopathy. It may completely recover following SK administration.

Figure Legend

Endomyocardial biopsy findings from pt 5 with PS-related myocarditis including histology (panel A). Immune-histochemistry for IL 17-A (panel B) and anti-heart abs (panels C, D). It shows an active lymphocytic myocarditis with overexpression of IL 17-A and positive anti-heart abs (panel C), cross-reacting with skeletal muscle (panel D).
Diabetes and chronic kidney disease synergistically contribute to left ventricular diastolic dysfunction and coronary microvascular disease in swine
Authors: Hamers J , Sittig T , Bierschenk S , D'alessio C , Zhang H , Clauss S , Schuettler D , Tomsits P , Vlcek J , Pauly V , Hesse N , Sen P , Merkus D
Published: November 2023

Background

Chronic kidney disease (CKD) and diabetes (DM) are common causes of cardiovascular disease (CVD), and contribute to the development of left ventricular diastolic dysfunction (LVDD) and coronary microvascular dysfunction (CMD).

Purpose

To investigate if CKD and DM contribute synergistically to the development of CMD and LVDD by increasing myocardial interstitial fibrosis in a swine model.

Methods

CKD was induced by renal microembolization at 10-12 weeks of age in 8 wild type (WT) and 6 DM (INSC94Y) swine, while 6 WT and 5 DM swine served as control. LVDD was assessed using pressure volume loops and coronary flow reserve (CFR) was measured by intracoronary infusion of adenosine in the left anterior descending coronary artery. Afterwards, myocardium and kidney tissues were histologically examined for interstitial fibrosis.

Results

DM was confirmed by increased blood glucose values in the DM and DMCKD (figure 1-A). Renal embolization resulted in renal fibrosis in the WTCKD and DMCKD (figure 1-B), which was accompanied by a trend towards proteinuria, i.e., elevated protein/creatinine ratios (figure 1-C). LVDD was evidenced by an increase in the slope of the end-diastolic pressure volume relationship (EDPVR) in WTCKD, DM and DMCKD as compared to WT, with the largest increase in DMCKD (figure 1-D). WTCKD and DMCKD animals showed higher interstitial fibrosis levels in the LV (figure 1-E). CFR tended to be decreased in WTCKD, DM and DMCKD swine compared to WT (figure 1-F).

Conclusions

Renal embolization resulted in proteinuria and renal fibrosis, particularly in DM animals. DM and CKD also caused myocardial interstitial fibrosis, which impaired left ventricular diastolic function. The effects tended to be larger in DMCKD as compared to DM or WTCKD. Moreover, CFR tended to be decreased, suggestive of CMD, with the largest effect in DMCKD. In conclusion, DM and CKD contributed synergistically to LVDD and CMD.
Epicardial tissue derived leptin promotes myocardial injury in metabolic syndrome rats through PKC/NADPH oxidase/ROS pathway
Authors: Chen H , Tian G
Published: November 2023

Background

The epicardial adipose tissue (EAT) of metabolic syndrome (MetS) is abnormally accumulated with dysfunctional secretion of adipokines, closely relating to cardiac dysfunction. The adipokines leptin has been proven to induce cardiac fibroblasts collagen metabolism disorder in hypertensive left ventricular hypertrophy rats.

Purpose

The study was designed to identify the effects of EAT-derived leptin on the myocardium of MetS rats and explore the potential molecular mechanisms.

Methods and results

MetS rat model was established in eight-week-old male Wistar rats by 12 week high-fat diet. MetS rats exhibited increased leptin secretion from EAT, cardiac hypertrophy and diastolic dysfunction with preserved systolic function. The myocardium of MetS rats had abnormal structure and mitochondrial morphology, increased oxidative stress injury and inflammatory factors level, especially the subepicardial myocardium, which was correlated with the EAT-derived leptin level, but not the serum leptin (Figure 1). The EAT was separated from each group rats to prepare EAT-Conditioned Medium (EAT-CM). The H9C2 rat cardiomyoblasts were treated with EAT-CM or leptin, plus various signaling pathway inhibitors. EAT derived leptin from MetS rats promoted mitochondrial oxidative stress and dysfunction, induced mitochondrial pathway apoptosis and inhibited cell viability in H9C2 cardiomyoblasts via PKC/NADPH oxidase/ROS pathway. EAT derived leptin from MetS rats stimulated inflammation in H9C2 cardiomyocytes by promoting AP-1 nuclear translocation via PKC/NADPH oxidase/ROS pathway. Leptin promoted the interaction between p-p47phox and gp91phox in H9C2 cardiomyocytes via PKC, activating NADPH oxidase, increasing ROS generation, and inhibiting cell viability.

Conclusions

EAT derived leptin induces the MetS related myocardial injury though the following two cooperative ways via PKC/NADPH oxidase/ROS pathway: 1. Inducing mitochondrial pathway apoptosis by promoting mitochondrial oxidative stress and dysfunction; 2. Stimulating inflammation by promoting AP-1 nuclear translocation (Figure 2). The results reveal the potential molecular mechanisms of EAT in MetS related myocardial injury, providing novel insights for the further study of MetS related cardiovascular diseases.Figure 1Figure 2
Long-term clinical-pathologic results of enzyme replacement therapy in pre-hypertrophic Fabry disease cardiomyopathy
Authors: Frustaci A , Verardo R , Galea N , Alfarano M , Magnocavallo M , Scialla R , Sansone L , Belli M , Cristina M , Frustaci E , Russo M A , Chimenti C
Published: November 2023

Background

Limited ability of ERT in removing Gb-3 from cardiomyocytes is recognized for advanced FDCM. Pre-hypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available.

Purpose

Long-term clinical-pathologic impact of ERT on pre-hypertrophic FDCM.

Methods

Fifteen Fabry patients with LVMWT ≤ 10.5 mm at CMR required EMB because of angina and/or ventricular arrhythmias. EMB showed coronary small vessel disease in angina cohort and vacuoles in smooth muscle cells and cardiomyocytes around 20% of cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 and β-agalsidase in 7 cases. Both groups referred symptoms improvement except 2 patients treated with α- and β-agalsidase respectively. After ERT administration ranging from 4 and 20 years all patients had control CMR and LVEMB because of persistence of symptoms or patients enquiry on disease resolution.

Results

In 13 asymptomatic FDCM patients, LVMWT and LV-mass, cardiomyocyte diameter, vacuole surface/cell surface ratio and vessels remained unchanged even after 20 years observation and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed with larger and more engulfed by Gb-3 myocytes being associated to myocardial virus-negative lymphocytic inflammation.

Conclusions

ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with pre-hypertrophic FDCM. Gb-3 is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap limiting ERT activity.

Figure legend

Long-term ERT effects on FDCM.

ERT improves symptoms, stabilizes storage deposits and left ventricular mass index in 87% of patients with pre-hypertrophic FDCM. In 13% of patients there is a progression of the disease in spite of ERT, with a superimposed immune-mediated myocardial inflammation at EMB.
Prognostic significance and pathophysiological insights of functional phenotypes clustering
Authors: Bandera F , Mollo A , Boveri S , Alfonzetti E , Milani V , Ambrogi F , Guazzi M
Published: November 2023

Background

Functional capacity (FC) is a marker of cardiorespiratory fitness reflecting the integrity of cardiac, respiratory and peripheral metabolic systems. Cardiopulmonary exercise test (CPET) is the method of reference to quantify the functional capacity through a multiparametric approach. Functional phenotypes can be identified according with the patterns of CPET variables. We sought to explore the prognostic role of CPET-derived functional phenotypes, identified by an automatic clustering process, and to understand the underlying cardiac pathophysiology as assessed by exercise-echocardiography (Exe-Echo).

Methodology

1379 unselected subjects who underwent to CPET combined with Exe-Echo were included in the study. Cluster analysis based on CPET variables (% of predicted peakVO2, anaerobic threshold, VE/VCO2, peak respiratory ratio, chronotropic index, O2 pulse, peak PetCO2, VO2/WR slope and heart rate recovery) identified 4 clusters (C1= 207, C2= 546, C3= 475, C4= 151 subjects), differing primarily for a progressive worsening of FC (% of PeakVO2: 87±18, 75±13, 60±14, 48±13%; VE/VCO2 25.3±2.7, 26.5±3.0, 30.8±4.3, 39.4±7.8; in C1, C2, C3, C4 respectively, all p<.001). Rest and exercise parameters of Exe-Echo were used to define cardiac characteristics and presented in a standardized radar clustering (fig 1). Patients were tracked for the combined end-point of death + heart failure hospitalization.

Results

C1 presented normal cardiac morphology and function with expected increase of stroke volume (SV) and cardiac output (CO) during exercise, without significant valvular disease; C2 and C3 showed a mild-to-medarately abnormal rest and exercise echo parameters, characterized by LV progressive dilatation, mild systolic dysfunction, mitral regurgitation (MR) and increased systolic pulmonary pressure (SPAP); C4 corresponded to severe cardiac remodelling with LV and left atrial enlargement, severe MR, rest pulmonary hypertension and severely impaired contractile reserve (reduced exercise SV and CO). The 4 clusters were strongly associated with prognosis, as shown by KM of survival free from combined event (p<.0001; fig 2).

Conclusions

automatic clustering of CPET parameters identified 4 clusters strongly associated with hard end-points (mortality and HF hospitalization). Exe-Echo provided cluster-related pathophysiological insights explaining the mechanisms responsible for prognosis decline. This combined CPET-ExeEcho approach may help in identifying high risk patients and in defining new therapeutic targets.Radar chart of echo variablesKM of combined end-point (death+HF)
Histidine triad nucleotide-binding protein 2 deficiency induce myocardial glucose utilization disorder in mice
Authors: Fan M K , Yao L H , Huang Y , Sheng H Z
Published: November 2023

Introduction

Histidine triad nucleotide-binding protein 2 (HINT2) has been shown to be benefit to energy metabolism after myocardial infarction. However, the exact mechanism of HINT2 in myocardial metabolism remains unclear.

Purpose

To explore the effect of HINT2 deficiency on cardiac function and metabolic profile.

Methods

HINT2-/- mice was generated for experiment in vivo by CRISPR/Cas9 technique. Neonatal mouse ventricle myocytes were used for in vitro experiment. Transthoracic echocardiography and histological analyses were performed to assess ventricle structure and function. Transmission electron microscopy was used to observe ultrastructure in ventricle tissues. Conjoint analysis of proteomics and metabolomics was to screen the metabolism profile and signal pathway. Seahorse XFe 96 analysis was performed to detect oxygen consumption rates and glycolysis rate. Immunoprecipitation mass spectrometry was used to explore the HINT2-interacting protein. Co-immunoprecipitation and proximity ligation assay were used to detect the interaction between proteins.

Results

Comparing to HINT2+/+, HINT2 deficient mice had higher level of left ventricular posterior wall thickness, and lower left ventricular ejection fraction. The heart weight/tibia length, cross-sectional area and cardiac fibrosis area were increased in HINT2 deficient mice. In HINT2 deficient, using transmission electron microscopy, thicker cardiac muscle fibers was observed, with disorganized and disorganized mitochondria. Conjoint analysis of proteomics and metabolomics exhibited the network of differential protein and metabolite, which proved HINT2 deficiency activated the pathway of diabetic cardiomyopathy. Immunoprecipitation showed that the level of glycosylated modification in heart tissues was higher in HINT2 deficient mice. Seahorse analysis showed that the basal and max oxygen consumption rate in HINT2 deficient mice was significantly lower, and so was the mitochondria related Proton efflux. With immunoprecipitation mass spectrometry detection, we found that PDK4 may have interaction with HINT2. Both co-immunoprecipitation and proximity ligation assay proved that HINT2 and PDK4 has interaction and subcellular localization.

Conclusions

HINT2 plays an important role in cardiac function and glucose metabolism, which is a critical molecule in process of diabetic cardiomy.
Disturbance of iron metabolism related genes in advanced heart failure
Authors: Tarazon E , Perez Carrillo L , Madejon M , Gimenez Escamilla I , Delgado Arija M , Gonzalez I , Portoles M , Rosello-Lleti E
Published: November 2023

Background/Introduction

Heart failure (HF) is a clinical syndrome associated with poor quality of life, substantial health-care resource utilization, and premature mortality. Iron is a nutrient required in all organ systems for various metabolic processes, such as mitochondrial function, oxygen transport, myocardial and skeletal muscle metabolism, among others. Maintaining iron homeostasis is essential for proper cardiac function since both iron deficiency and iron overload are associated with HF through complex mechanisms, such as ferroptosis.

Purpose

The aim of this study was to analyse the status of iron metabolism in hearts from patients with dilated (DCM) and ischemic cardiomyopathy (ICM) and its implication with the pathophysiology of the disease.

Methods

Cardiac tissue samples were used to evaluated transcriptome differences in genes involved iron metabolism by mRNA-sequencing (mRNA-seq; ICM, n=13; DCM, n=13; CNT, n=10). Furthermore, the miRNA implicated in the mRNA posttrasciptional regulation was studied through non-coding RNA-seq (ICM, n=22; DCM, n=20; CNT, n=8).

Results

We observed a decrease in iron import with SNX4 underexpression in ICM (FC=-1.28) and DCM (FC=-1.27) patients, p<0.05. While the export is reduced only in patients with MCD: HAMP is underexpresed (FC=-2.41, p<0.01) and its miRNA, miR-184, overexpressed (FC=2.77, p<0.01). We also found alterations in molecules of iron homeostasis and transporters of both aetiologies: IREB2 (ICM, FC=-1.27, p<0.05; DCM, FC=-1.48, p<0.001), STEAP3 (ICM, FC=-1.63, p<0.05; DCM, FC=-2.24, p<0.001), NOX4 (DCM, FC=1.70, p<0.05), SLC39A14 (ICM, FC=-1.97, p<0.05) and SLC39A8(ICM, FC=-1.60, p<0.05; DCM, FC=-1.78, p<0.01). Myoglobin was increased (FC=1.18, p<0.05) and its miRNA, miR-133a-3p, decreased (FC=-1.39, p<0.05) in DCM patients. While other molecules implicated in iron metabolism such as NFE2L2 (ICM, FC=-1.52; DCM, FC=-1.30; p<0.05) and AGPAT5 (ICM, FC=-1.84, p<0.05) are decreased. It is worth noting the correlation with ventricular dysfunction shown by SLC39A8 (end systolic diameter, r=-0.674; end diastolic diameter, r=-0.648; p<0.05) in ICM patients and NFE2L2 (ejection fraction, r=0.609, p<0.05) in DCM patients.

Conclusions

Our results show an alteration in the iron metabolism specific of aetiology in HF, both in the genes involved in different functions of the pathway and in its post-translational regulation. These results offer new possible therapeutic targets and valuable information to elucidate the complex mechanisms that relate iron homeostasis to HF.