bluuebunny/crossref_metadata_2025_split huggingface dataset:
LDL electronegativity and male predominance in early ventricular tachyarrhythmias following ST-elevation myocardial infarction: evidence of sexual dimorphism associated reduction of sodium currents
Authors: Chang K C , Wu M Y , Lin Y N , Lee A S , Chen C H 
Published: November 2023

Abstract

Background
Early ventricular tachycardia/fibrillation (VT/VF) in patients with ST-elevation myocardial infarction (STEMI) was associated with a higher morbidity and mortality rate. We sought to investigate the gender-specific risk and explore the underlying mechanisms of early VT/VF in STEMI patients.

Methods
We analyzed the clinical and laboratory data among 2965 consecutive STEMI patients between Jan 1, 2008 and Dec 31, 2021. Early VT/VF was defined as occurrence of spontaneous VT/VF of ≥30 seconds or requirement of immediate cardioversion/defibrillation due to hemodynamic compromise within the first 48 hours after onset of symptoms. To explore the mechanisms underlying early VT/VF, ex vivo ischemic-reperfusion experiments were conducted in 8-week-old ApoE-/- mice fed a high-fat diet for 8 weeks to promote atherogenesis.

Results
Of the 2965 STEMI patients studied, 256 (8.6%) experienced early VT/VF. Patients who developed early VT/VF were younger (58±13 vs. 61±13 years old, P=0.012) and had a higher proportion of males (87% vs. 83%, P=0.043). Notably, some patients with early VT/VF had significantly higher plasma levels of L5, the most electronegative subclass of low-density lipoprotein (LDL), compared to those without early VT/VF (n=19, L5: 10.14±3.09% vs. n=43, L5: 2.11±0.23%, P=0.006). In animal study, we have previously showed that male mice have higher plasma L5 concentrations than female mice. In this study, all male mice (n=4) developed VT/VF following the sham operation, whereas none of the female mice (n=3) did. Moreover, male mice had significantly slower heart conduction velocity than female mice in whole heart preparations (13.37±3.81 cm/s vs. 40.70±4.97 cm/s, P&lt;0.001), despite having similar action potential duration (61.00±7.07 vs. 50.33±4.16 ms, P=0.999). In addition, isolated ventricular myocytes from male mice exhibited markedly lower sodium current density (-29.20±3.04 pA/pF, n=6) compared to those from female mice (-114.05±6.41 pA/pF, n=6, P&lt;0.001). The reduced sodium current density was accompanied by lower membranous Nav1.5 protein expression (0.38±0.06 vs. 0.89±0.09 A.U., P&lt;0.001) and higher cytosolic Nav1.5 levels (0.59±0.06 vs. 0.29±0.04 A.U., P&lt;0.01) in male mice.

Conclusions
Our study demonstrates that male STEMI patients with early VT/VF have higher levels of L5, the most electronegative LDL subclass. This gender disparity in the susceptibility of early VT/VF may be caused by compromised sodium channel trafficking, likely linked to increased LDL electronegativity.
Long-term follow-up in patients with hypertrophic cardiomyopathy after defibrillator implantation: analysis of appropriate and inappropriate therapy
Authors: Basse Christensen E , Vissing C R , Silajdzija E , Mills H L , Thune J J , Bosselmann H , Larroude C E , Philbert B T , Raja A A , Christensen A H , Bundgaard H 
Published: November 2023

Abstract

Background
Treatment with implantable cardioverter-defibrillators (ICD) is effective for prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). Assessment of SCD risk and identification of patients most likely to benefit from primary prevention ICD is challenging.

Purpose
To investigate the long-term incidence of appropriate and inappropriate ICD therapy in patients with HCM.

Methods
This was a retrospective cohort study including all patients with HCM and ICDs implanted between 1995 to 2022 in our region (population 2.6 million). Both patients treated with primary and secondary prevention ICD were included. Data was retrieved from medical records. Patients with an ICD implanted for primary prevention were stratified into risk groups according to European Society of Cardiology HCM Risk-SCD score.

Results
We included 187 patients (65% male) with HCM and ICDs implanted for primary (80%) or secondary (20%) prevention. The median age at ICD implantation was 50 years (IQR: 40 to 61 years). During a mean follow-up of 9 years (IQR: 4 to 12 years), 53 patients (28%) experienced appropriate ICD therapy (antitachycardia pacing and/or shock), while 17 (9%) patients received inappropriate therapy. Patients with an ICD as secondary prevention were almost twice as likely to receive appropriate ICD therapy compared to patients with a primary prevention ICD (42% vs. 25%, p=0.04). The proportion of patients receiving appropriate shocks was 7 times higher in patients with an HCM Risk-SCD score ≥6% compared to patients with a risk score &lt;4% (29% vs. 4%, p&lt;0.001). There was no significant difference in the proportion of appropriate shocks between patients with a HCM Risk-SCD score ≥6% and patients with a risk score of 4%-6% (29% vs. 21%, p=0.49). (Figure 1).

Conclusion
One in four patients with HCM treated with an ICD experienced appropriate device intervention during 9 years of follow up. Patients with an HCM Risk-SCD score ≥6% had a 7-fold higher risk of appropriate ICD therapy compared to patients with an HCM Risk-SCD score &lt;4%. There was no significant difference in the risk of appropriate shock therapy between patients with a risk score ≥6% and patients with a risk score of 4%-6%. The findings indicate the need for improved selection of patient with HCM for implantation of ICD’s.
Ventricular arrhythmia outcomes in hypertrophic cardiomyopathy from a high level myectomy centre
Authors: Gupta M , Naser A , Doyle M , Williams R B , Okasha O , Biederman R W W 
Published: November 2023

Abstract

Background
The presence of ≥15% late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (MRI) is used as a prognostic indicator for sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). [1] According to the European Society of Cardiology clinical practice guidelines (2014), septal myectomy is only indicated for symptomatic relief from left ventricular outflow tract obstruction (LVOTO) that is refractory to medical therapy, provided LVOTO gradient ≥ 50 mmHg. [2] At present, there is scarce data correlating the burden of ventricular arrhythmia and sudden cardiac death with LGE percentage or showing benefit of myectomy in reducing the burden of the same.

Purpose
We aimed to compare the burden of ventricular arrhythmia burden in patients with HCM who underwent septal myectomy compared with those who did not.

Methods
Adult patients with HCM followed in the advanced heart failure outpatient clinic at Allegheny General Hospital were included in this study. All included patients had cardiac MRI with LGE quantification and data related to cardiac events through devices placed for various indications (such as evaluation of reported palpitations, established supraventricular tachycardia, implantable cardioverter-defibrillator for primary or secondary prevention). Patients were divided into 2 groups: those undergoing myectomy (post myectomy group) and those that did not undergo myectomy (non-myectomy group). Chi square test was used to calculate incidence of premature ventricular contractions (PVCs), non-sustained ventricular tachycardia (NSVT) and sustained ventricular tachycardia (SVT) in the non-myectomy and post myectomy group.

Results
76 patients with HCM (interventricular septal thickness ≥1.5 cm and LGE positive) longitudinally followed in the Allegheny General Hospital advanced heart failure outpatient clinic from 2016 to 2022 were included. 37 patients underwent septal myectomy. Baseline characteristics of post myectomy and non-myectomy group were matched and are listed in table 1. Left ventricular mass index was expectedly higher in patients undergoing myectomy. LGE was quantified on cardiac MRI prior to myectomy (mean 16.4% in myectomy group, 14.6% in non-myectomy group). Burden of ventricular arrhythmia (PVCs, NSVT and SVT) was found to be significantly lower in the post myectomy group (n=13, 44.83%) compared to the non-myectomy group (n=36, 92.31%). None of the patients included were noted to have ventricular fibrillation or sudden cardiac death.

Conclusion
Septal myectomy may reduce the incidence of ventricular arrhythmia and thus impact outcomes related to sudden cardiac death. This is likely a consequence of removal of arrhythmogenic scar tissue. Larger studies are required to further evaluate the burden and correlation of ventricular arrhythmia with scar tissue volume measured on cardiac MRI.
X-linked Emery-Dreifuss muscular dystrophy is associated with a high risk of malignant ventricular arrhythmia
Authors: Cannie D , Syrris P , Rodriguez-Palomares J F , Marini-Bettolo C , Mestroni L , Parikh V N , Barriales-Villa R , Jiminez-Jaimez J , Garcia-Pavia P , Charron P , Biagini E , Garcia-Pinilla J M , Savvatis K , Wahbi K , Elliott P M 
Published: November 2023

Abstract

Background
Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (X-linked) and LMNA (autosomal dominant). LMNA variants are known to cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA) [1], but the risk of cardiac complications in EMD variant-carriers is unknown.

Purpose
To determine the incidence of MVA and ESHF in EMD variant-carriers.

Methods
Consecutively referred individuals carrying EMD variants were recruited from 12 cardiomyopathy units in Europe and the USA. The incidence of MVA and ESHF in male and female EMD variant-carriers was determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDcardiac) were compared to consecutively recruited male LMNA variant-carriers with a cardiac phenotype (LMNAcardiac).

Results
Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers (mean (SD) ages 33.4 (13.3) and 43.3 (16.8) years, respectively; Table 1). Nine (23.6%) males developed MVA and five (13.2%) developed ESHF during a median follow-up time of 65.0 [24.3, 109.5] months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a mild cardiac phenotype at a median [IQR] age of 58.6 [53.2, 60.4] years.
Incidence rates for MVA were similar for EMDcardiac and LMNAcardiac (4.8 versus 6.6 per hundred person-years, respectively; log-rank test p = 0.49; Figure 1). Incidence rates for ESHF were 2.4 per hundred person-years for EMDcardiac and 5.9 per hundred person-years for LMNAcardiac (log-rank test p = 0.09; Figure 1).

Conclusions
Male EMD variant-carriers have a high risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. These data suggest that early ICD implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease.Table 1Figure 1
Monitoring the electrophysiological effects of hydroquinidine non-invasively in patients with Brugada syndrome
Authors: Isbister J C , Strocchi M , Chiswell K , Yeates L , Cham J , Gray B , Ingles J , Semsarian C , Raju H , Neiderer S , Sy R 
Published: November 2023

Abstract

Background
Quinidine and it’s derivative hydroquinidine are the only drugs shown to reduce arrhythmic events in patients with Brugada syndrome (BrS). There is currently no standardised approach to monitoring the effect of pharmacotherapy in BrS to guide dosing and evaluate an individual’s response to therapy.

Purpose
To investigate if the electrophysiological effects of Hydroquinidine can be detected on non-invasive testing and identify parameters that may be used to study a non-invasive strategy for monitoring pharmacotherapy in BrS.

Methods
Patients with a diagnosis of BrS underwent multimodality non-invasive assessment with electrocardiogram (ECG), signal averaged ECG, 24 hour 12-lead Holter monitor and electrocardiographic imaging (ECGi – a method of non-invasive electroanatomical mapping), at baseline and "on treatment" with hydroquinidine (300mg BD) therapy. A medication survey was used to recorded adverse drug reactions and serum hydroquinidine levels were determined using liquid chromatography mass spectrometry.

Results
Twelve patients with BrS (11 male, mean age 47.6±10.9 years) with spontaneous type 1 BrS pattern or drug inducible type 1 BrS pattern and resuscitated cardiac arrest participated in the study. The mean Shanghai score was 4.6±1.4 and two patients had disease-causing SCN5A variants. During hydroquinidine therapy, there was a significant increase in QRS duration (110.7msec vs 117.8msec, p=0.004) and in mean activation time in the area of late activation in the right ventricular outflow tract (RVOT, 90.9ms to 97.7ms, p=0.020). In nine (75%) patients, the area of late activation (defined as &gt;80ms after initial activation) in the RVOT also increased with hydroquinidine. Repolarisation parameters were also affected by hydroquinidine with an increase in QT interval corrected for heart rate (369.5msec vs 434.8msec, p&lt;0.0001) and T-wave width (232.8msec to 271.2msec p=0.003) and a significant reduction in T-wave amplitude (0.4mV to 0.2mV p=0.001) on treatment. The reduction in T-wave amplitude precluded computation of repolarisation time in the RVOT by ECGi on treatment. No difference in the burden of type 1 BrS ECG pattern over 24 hours was seen on 12-lead Holter monitor between baseline and on treatment assessment. No significant difference in serum hydroquinidine level was detected between those who experienced side effects and those who did not (2.9µmol vs 3.1µmol, p=0.790).

Conclusion
Hydroquinidine affects both ventricular activation and repolarisation in patients with BrS and these effects can be detected non-invasively. Further work is required to determine clinical significance of these observed effects and investigate the feasibility of non-invasive monitoring strategy of pharmacotherapy in BrS.ECGi activation maps
New risk predictor of arrhythmias in patients with congenital Long-QT Syndrome
Authors: Juarez Krijger C , Proost V , Tanck M W T , Dittmann S , Schulze-Bahr E , Schwartz P J , Bezzina C R , Wilde A A M 
Published: November 2023

Abstract

Congenital long-QT syndrome (LQTS), is an inherited cardiac channelopathy characterized by delayed ventricular repolarization, which may lead to Torsade de pointes (TdP), that may degenerate into ventricular fibrillation. Determination of risk remains unrefined. It is well established that the repolarizing current Iks is increased during adrenergic stimulation, as occurs during exercise, thereby playing an important role in shortening the QT interval as an adaptation to increased heart rate. Accordingly, patients with LQTS, in particular those with LQT1 are at high arrhythmic risk during exercise. We hypothesized that changes in QTc during exercise stress test (EST) may be useful for risk stratification in LQTS. Furthermore, we hypothesized that as changes in IKs impact on repolarization reserve, the predictive capacity of the EST may extend to other LQTS genetic subtypes.

Aim
assessing the potential value of QT dynamics during EST to identify high risk patients in patients with LQT1 and LQTS2.

Methods
This study included genotype-positive LQT1 and LQT2 patients from the Netherlands, Italy and Germany. Symptomatic patients; patients whom experienced an arrhythmic syncope, sustained ventricular arrhythmia or (aborted) sudden cardiac death. Twelve-lead ECGs were digitally acquired during exercise testing. QT measurements were determined at specific time points. Statistical analyses were performed using R software. Logistic regression and cox proportional hazards models were used to calculate the predictive value and hazard ratio per ms increase in ΔQTc. Covariates included age, QTc, sex, beta-blocker use, center and genetic variant location.

Results
A total of 222 patients with LQT1 and 164 patients with LQT2 (Table 1), with a pathogenic or likely pathogenic variant in KCNQ1 or KCNH2, were included. In both LQTS1 and LQTS2 patients, the ΔQTc between rest and at 3-4 minutes recovery was the most relevant and significant EST predictor.
For LQT1, the ΔQTc was significantly increased in symptomatic patients versus non-symptomatic ones (46 ms ± 35 vs 18 ms ± 36, p = &lt; 0.001)(figure 1 panel A). Logistic regression model shows a predictive value (AUC) of 89.2% for ΔQTc. Survival analysis showed a hazard ratio of 1.02 with 95% CI of 1.01 – 1.03 for each ms ΔQTc increase.
For LQTS 2 patients, the ΔQTc between rest and 3-4 minutes recovery was also increased in symptomatic patients versus non-symptomatoc ones (27 ms ± 40 vs 12 ms ± 40, p = 0.03). Logistic regression analysis; OR per ms: 1.02 (1.01 – 1.04 95%CI) AUC 78.3%. Survival analysis showed a hazard ratio of 1.02 (1.01 - 1.03 CI) for each ms ΔQTc increase.

Conclusion
The ΔQTc between rest and at 3-4 minutes recovery was significantly increased in symptomatic LQT1 and LQT2 patients compared to non-symptomatic patients, and is a promising risk marker to identify high risk patients, in both LQT1 and LQT2.Table 1
Insights regarding in-hospital outcomes of COVID-19 hospitalisations and co-existing premature ventricular contractions : from national inpatient sample 2020
Authors: Gajjar R , Teaima T , Battikh N , Aziz I , Shoura S , Sad Aldeen Z 
Published: November 2023

Abstract

Introduction
Since the emergence of the COVID-19 pandemic, several reports have highlighted COVID-19 infection's arrhythmogenic consequences on the cardiac conduction system (1). SARS-CoV-2 has a well-established predilection to cardiomyocytes and is associated with myocardial injury with worse predicted outcomes. A wide range of electrocardiographic findings was significantly associated with COVID-19 infection (2). However, literature is scarce on the outcomes of such ECG findings, and its implications are yet to be understood.

Purpose
We sought to illustrate the significant outcomes of patients hospitalised for COVID-19 infection and premature ventricular contractions.

Methods
The National Inpatient Sample database (NIS) - 2020 was analysed to identify adult hospitalisations with a primary diagnosis of COVID-19 with or without co-existing premature ventricular contractions (PVC) using International Classification of Diseases – 10 Clinical Modification (ICD-10-CM) codes. The primary outcome was inpatient mortality, while secondary outcomes included inpatient morbidity, mean length of stay (LOS), and mean total hospital charge (THC). Multivariate logistic regression and linear regression analyses were used to adjust for possible confounders.

Results
Out of 1,050,045 COVID-19 hospitalisations, 7,729 (0.73%) had PVCs. Encounters with COVID-19 and co-existing PVCS had higher adjusted odds of inpatient mortality (Adjusted odds ratio [aOR]: 1.18, 95% confidence interval [CI]: 1.014-1.38, p=0.033), longer mean LOS of 1.8 days (95% CI: 1.4-2.3, p &lt;0.001), and higher mean THC of $21,869 (95% CI: $13,902-$29,835, p &lt;0.001) than those without co-existing PVCs. Figure 1 shows a forest plot illustrating the multivariate analysis of in-hospital morbidities when adjusted for patient demographics, comorbidities, and hospital characteristics.

Conclusion
Among patients hospitalised with COVID-19 infection, those with premature ventricular contractions had worse outcomes regarding in-hospital mortality, sepsis, need for endotracheal intubation, mechanical ventilation, and vasopressors use, in addition to the longer length of hospital stay, and higher total hospital charges. Although PVCs are commonly encountered in hospitalised patients and often require no medical interventions in most cases, they are associated with poor prognosis in patients with COVID-19 infection.Forest plot for adjusted outcomes
Predictors of and outcomes in arrhythmic mitral valve prolapse
Authors: L'hoyes W , Robyns T , Moura-Ferreira S , De Meester P , Dresselaers T , Herregods M C , Rega F , Masci P G , Willems R , Bogaert J , Vandenberk B 
Published: November 2023

Abstract

Background
Recently, the European Heart Rhythm Association (EHRA) defined the phenotype of the arrhythmic mitral valve prolapse (AMVP) complex and proposed management approaches. Assessing the incidence of SCD in this small subset of patients is challenging due to the low event-rate and longitudinal real-world data remain scarce.

Purpose
To determine the predictors of AMVP and study the clinical outcome of patients stratified by ICD indication as proposed by the EHRA consensus statement.

Methods
All consecutive patients with MVP who underwent cardiac magnetic resonance imaging (CMR) were enrolled in a single-center retrospective registry. AMVP was defined as the presence of frequent or complex ventricular arrhythmias (&gt;5% total PVC burden, non-sustained ventricular tachycardia (VT), VT or ventricular fibrillation) in a patient with MVP without alternative arrhythmic substrates. The medical records of these patients included a comprehensive clinical, rhythmic and echocardiographic characterization allowing to collect the key date of transition to AMVP. A forward conditional multivariable logistic regression was performed to identify clinical risk factors for AMVP reporting the odds ratio (OR) and corresponding 95% confidence interval (95% CI). Incidence rates were calculated for the composite endpoint of SCD, sustained VT, ICD shocks, and all-cause mortality.

Results
A total of 169 patients (52.1% male, median age 51.4 years) were included, of which 99 (58.6%) were classified as AMVP. Clinical characteristics are presented in Image 1. Patients with non-arrhythmic MVP and AMVP had comparable left ventricular function, mitral valve regurgitation grade and extent of MVP. Multivariable logistic regression identified the presence of late gadolinium enhancement (LGE, OR 2.82, 95%CI 1.45–5.50, p=0.002) and mitral annular disjunction (MAD, OR 1.98, 95%CI 1.02–3.86, p=0.045) on CMR as only predictors of AMVP. Cardiac CMR results are presented in Image 2. The median overall follow-up since first cardiac contact was 8.0 years (IQR 5.0–15.6), while this was 5.0 years (IQR 2.1–7.4 years) after transition to AMVP. The incidence for the composite endpoint in the overall population was 0.4%/year (95%CI 0.2 – 0.9). The 5-year cumulative event rate was 1.8%. According to the EHRA risk stratification the implantation of an ICD would have been reasonable in 69 patients (69.7%). In total, 5 patients were implanted with an ICD for secondary prevention, but all those patients did not classify as AMVP prior to the life threathening arrhythmic event.

Conclusion
CMR is an important tool in the challenging risk stratification of AMVP given that the presence of MAD and LGE enhancement are predictors of AMVP. There is a lack of longitudinal data to determine when patients transition from MVP to AMVP and how this modifies their outcome.Clinical characteristics and ECG resultsOverview of CMR measurements