bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of real-world off-label dose of Apixaban on long-term clinical outcomes in patients with atrial fibrillation and chronic kidney disease
Authors: Im S I , Shin H S
Published: October 2024

Background

Apixaban represent one of the cornerstone treatments to prevent cardioembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the choices of Apixaban dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice.

Objective

The objective of the present study is to evaluate the effects of real-world Off-label dose of Apixaban on long-term clinical outcomes in NVAF patients with chronic kidney disease (CKD).

Methods

Our database of AF patients diagnosed with CKD from 2018 to 2023 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all AF patients with CKD using Apixaban. And we compared bleeding, systemic thrombotic events including stroke/systemic embolism and death according to off-label real -world dose of Apixaban.

Results

Among 635 patients with AF and CKD (76.9±10.4 years), 335 (52.8%) patients took off-label underdosed Apixaban. Difference in the baseline characteristics was not observed among patients including CHA2DS2 VASc score and HASBLED score. During the median 18-month follow-up, a lower incidence of bleeding events (P=0.001) was observed in the off-label underdosed Apixaban group compared to those with standard dose or off-label overdosed Apixaban. However, there was no significant difference of systemic thrombotic events including stroke/systemic embolism and death according to off-label real-world dose of Apixaban (off-label underdose vs. standard dose, P=1.000; off-label overdose vs. standard dose, P=1.000; off-label underdose vs. off-label overdose, P=0.609). In multivariate analysis, HASBLED score was independent risk factors for bleeding events (OR 9.650; CI 1.998-46.622; P=0.005).

Conclusions

Compared with standard or off-label overdose of Apixaban, off-label underdose of Apixaban was associated with a lower risk of bleeding in patients with AF and CKD, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing tailored to specific clinical features and drug pharmacokinetics of the Asian patients.
Evaluation of concordance and association with clinical outcomes across eGFR values calculated with eight different formulas in a large cohort of european patients with atrial fibrillation
Authors: Boriani G , Bonini N , Mei D A , Imberti J F , Romiti G F , Corica B , Gerra L , Mantovani M , Vitolo M , Proietti M , Lip G Y H
Published: October 2024

Background

In randomized clinical trials of Direct Oral Anticoagulants (DOACs), the assessment of renal function impairment glomerular filtration rate (eGFR) in patients with Atrial Fibrillation (AF) has predominantly utilized the Cockroft-Gault (CG) formula for estimating Creatinine clearance (CrCl). However, in clinical practice, several other formulas for estimating glomerular filtration rate (eGFR) are employed. Limited data exist regarding the evaluation and comparison of eGFR/CrCl in AF patients.

Objectives

This study aimed to assess the concordance in the categorisation of renal function in in 6 classes taking into account eight different formulas for eGFR/CrCl (CG, CKD-EPI, CG/body surface area [BSA], BIS1, LMK, EKFC, FAS, MDRD) and their associations with a composite outcome (Major Adverse Cardiovascular Events [MACE] and all-cause death) in AF patients.

Methods

A contemporary European AF patient registry was utilized, and eGFR/CrCl were calculated using CG, CKD-EPI, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. eGFR was categorized according to KDIGO classes, with CKD patients defined as having eGFR/CrCl <60 ml/min/m2. Concordance was estimated using weighted Cohen’s kappa. Associations were evaluated through adjusted Cox regression analyses for the composite outcome, and results were plotted as spline curves.

Results: A total of 8516 patients were included in the analysis (Median [IQR] age: 70 [63-77] years; 3518 women, 41.3%). Among the formulas, EKFC exhibited the highest median values of eGFR and the lowest prevalence of CKD patients, while BIS1 had the lowest median eGFR values, and the FAS formula led to the highest prevalence of CKD patients [Figure 1]. In the concordance analysis, CKD-EPI demonstrated the highest concordance with all other formulas, even if Cohen’s kappa for measuring the degree of concordance ranged from 0.61 to 0.88 [Figure 1]. In adjusted Cox regression analyses, all formulas were associated with an increased risk for the composite outcome, progressively as eGFR decreased. When plotted as spline curves, the associations with the composite outcome visually showed a similar behaviour of risks across eGFR values in all formulas compared to the CG spline [Figure 2].

Conclusions

Among AF patients, the CKD-EPI formula exhibited variable, but substantially good concordance with CG, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. All calculated eGFR values showed a strong association with the composite outcomes, similarly to the CG formula, with higher risk when renal function decreased.FIGURE 1FIGURE 2
Atrial fibrillation-related complications following short-term use of antibiotics in patients receiving NOAC or warfarin
Authors: Huang J , Tse H F , Lip G Y H , Yiu K H
Published: October 2024

Introduction

To study the association of antibiotics with ischaemic stroke/systemic embolism (IS/SE) in patients with atrial fibrillation (AF) receiving anticoagulants.

Methods

This retrospective population-based cohort study applied electronic health data from a territory-wide medical database. Data were collected for patients with AF who were prescribed non-vitamin K antagonist oral anticoagulants (NOAC) or warfarin between Jan 1, 2010 and Dec 31, 2018. We further identify the patients with and without use antibiotics (any classification of antibiotics with prescription period within 7 days) during the NOAC/warfarin treatment period. The primary outcome is IS/SE and the secondary outcomes including hemorrhagic stroke (HS) and all-cause mortality. Patients were followed up for a median of 3.7 years. A self-control case crossover design was adopted to compare the short-term association between use of antibiotics and outcomes of interest among NOAC and warfarin group.

Results

This study included 40221 patients, consisted of 30617 NOAC users and 9826 warfarin users, while 9604 patients in NOAC group and 3325 patients in warfarin group had concurrent antibiotics use. At baseline, 46.1% of patients in NOAC group were male and the mean (SD) age was 77.4 (9.8) years, and 56.2% of patients in warfarin group were male and the mean (SD) age was 73.8 (11.3) years. Short-term use of antibiotics is associated with increased risk of IS/SE, HS and all-cause mortality in both NOAC and warfarin groups (NOAC vs. warfarin group: IS/SE: hazard ratio [HR]:3.41 [95%CI, 2.78-4.18]; HR: 2.51 [95%CI, 2.00-3.14]; HS: HR: 2.22 [95%CI, 1.78-2.78]; HR: 2.53 [95%CI, 1.86-3.43]; mortality: HR: 1.96 [95%CI, 1.85-2.08]; HR: 1.87 [95%CI, 1.73-2.02]; all P < 0.001).

Conclusion

The findings of the present study suggest that the short-term antibiotics use was associated with an increased risk of IS/SE, HS and all-cause mortality among patients in both NOAC and warfarin group. These findings further suggest that use of antibiotics may indicate a higher risk of IS/SE, HS and death for patients with AF, even when receiving NOAC/warfarin and that further investigation is warranted.The study design.The odds ratios of different outcomes.
Impact of the underlying rhythm during cavotricuspid isthmus ablation on the incidence of future new-onset atrial fibrillation: insights from an international multi-centre registry
Authors: Katic J , Badertscher P , Mannhart D , Zeljkovic I , Pavlovic N , Ammann P , Reichlin T , Roten L , Spreen D , Knecht S , Krisai P , Kuehne M , Sticherling C
Published: October 2024

Background

Radiofrequency catheter ablation of the cavotricuspid isthmus (RF-CTI) is the estabslished treatment of typical atrial flutter (AFL). After RF-CTI for AFL patients without previously documented atrial fibrillation (AF) may also develop AF. It is unknown whether the presence or absence of AFL at the time of ablation can predict the future occurence of AF.

Purpose

To compare baseline characteristics, procedural data, and long-term follow-up (FU) of patients with AFL.

Methods

Consecutive patients with documented AFL undergoing RF-CTI were enrolled in a multi-center registry in five centers in two countries between February 2017 and July 2023. For patients with AFL, entrainment mapping was performed for confirming CTI dependent AFL. Patients were categorized into two groups, those with AFL and those with sinus rhythm (SR) during RF-CTI. FU data were collected, including clinical assessments, 12-lead electrocardiogram (ECG) and 24-hour Holter-ECGs during each visit.

Results

Of the 949 subjects, 36% were excluded from the analysis due to a history of AF. A total of 574 patients were included (mean age 68 +/- 11 yrs, 14% females), 62% presented in AFL group and 38 % SR group during CTI. Median FU was 364 days. Patients in AFL group were older (P < 0.029), more likely to have diabetes (P = 0.026), and were less frequently treated with antiarrhythmic drugs (P < 0.001). In the first 12 months of FU, 40% of the patients underwent three FU examinations, while 77% of the patients underwent at least one 24-hour Holter-ECGs during FU. In the Kaplan-Meier analysis patients in AFL group significantly less often developed AF during FU (log-rank, P < 0.016, central ). In the multivariate Cox regression analysis, sinus rhythm during ablation (hazard ratio 1.474; 95% CI 1.043-2.084; P = 0.028), male gender (hazard ratio 1.722; 95% CI 1.116-2.658; P = 0.014) and coronary artery disease (hazard ratio 1.711; 95% CI 1.145-2.555; P = 0.009) were identified as predictors for the occurence of AF during FU.

Conclusion

Over a one year follow-up, new onset AF occurs significantly less frequently in patients with ongoing atrial flutter during RF-CTI ablation.
Detection of hypotension in patients with syncope: combined tilt test and ambulatory blood pressure monitoring strategy in clinical practice
Authors: Ruiz G A , Makhoul S , Agustini M , Gos Re V N , Maza S , Zarate J A , Tombesi P , Salzberg S
Published: October 2024

Both ambulatory blood pressure monitoring (ABPM) and Tilt Test (TT) (a provocation method), can identify the hypotensive component that predisposes to syncope.

Objective

1)To establish a) the prevalence of confirmed hypotension (CHp) with both methods; b) the concordance between them.

Methods

Patients (pts) ≥18 years with syncope for whom it was decided to perform a TT were included. TT was performed for 45 min at 75 degrees. On a different day, within 15 days, an ABPM was performed (≥70 % adequate readings). Criteria: CHp: In TT: TT(+) or detection of systolic blood pressure (SBP) ≤ 100 mmHg during the study resulting from a drop from baseline; in ABPM: SBP ≤ 100 mmHg resulting from a drop ≥ 20 mmHg from the previous one. Only the awake periods were considered.

Results

61 pts (age= 62.5±16.8, female= 39 (64%); antihypertensive medications= 35 pts (57%); Cardiovascular history, except isolated hypertension= 29 pts (47%). The reported number of episodes was 4±4.4 (median=2). Syncope was post-prandial in 25 pts (41%) and probable reflex by the description in 28 pts (46%).

CHp during syncope was confirmed in 25 pts during TT and in 1 pt during ABPM. Positive responses to TT were: vasodepressor in 14 pts, mixed in 10 pts and disautonomic pattern in 1 pt. Average 24 h in ABPM was above 135 mmHg in 10 pts (16%). Seventy-nine per cent of the population (48 pts) presented ≥ 2 falls ≥20 mmHg of SBP during the waking period.

SBP ≤ 100 mmHg constituted ≥ 20% of awake measurements in 10 pts (16%). A post-prandial fall in SBT ≥ 20 mmHg was detected in 24 patients (39%). Of these, in 8 (13%), the achieved SBP was ≤ 100 mmHg. Table 1 shows the prevalence for CHp with both methods. Table 2 shows the concordance between TT and ABPM.

CHp was detected by TT or ABPM in 48 pts, i.e 79% of the population. Both studies were concordant in 32 pts (52%) (Cohen's kappa coefficient: 0.04). CHp was identified in 28% of pts only by TT and in 20% only by ABPM.

Conclusion

CHp was detected in ¾ of this population using a combined TT and ABPM strategy. They were complementary not only to establish a diagnostic suspicion, but also to guide the therapeutic management of these patients.CHp PrevalenceTT and ABPM Concordance
Mitral regurgitation improvement following left bundle branch pacing versus right ventricular septum pacing: a dedication to postoperative amelioration of mitral regurgitation
Authors: Shan L , Dai W L
Published: October 2024

Background

Mitral regurgitation (MR) is correlated with left ventricular (LV) remodeling and LV function in patients. Left bundle branch pacing (LBBP) exhibits a significant decline in MR in left bundle branch block (LBBB) and cardiomyopathy patients. This research aims to evaluate the influence of LBBP on MR in comparison to right ventricular septal pacing (RVSP) in patients with atrioventricular block (AVB) or sick sinus syndrome (SSS).

Methods

Sixty consecutive patients with SSS or AVB were enrolled if they underwent pacemaker implantation via LBBP or RVSP. Patients with a history of mitral valve surgery were excluded. Echocardiogram parameters were assessed to measure MR and LV remodeling as well as LV function at baseline and follow-up.

Results

Thirty-six patients (60 %; mean age: 70.39 ± 14.80 years; 61.1 % male) underwent successful LBBP, and 24 patients (40 %; mean age: 71.58 ± 10.91 years; 66.7 % male) underwent RVSP. The average follow-up duration was relatively comparable between the two groups. In comparison to RVSP, LBBP demonstrated significant changes in MR area, and severity at baseline and follow-up (P<0.05). LBBP independently predicted MR amelioration in patients who underwent pacemaker implantation (HR=0.289, CI=0.087–0.9961; P=0.043). At follow-up, the LBBP subgroup with moderate/severe MR exhibited significantly shorter lead-TVA-dist, higher left atrium (LA) diameters, and mitral E/A ratio (P<0.05) compared to the none/mild MR subgroup. In LBBP with MR amelioration, LV remodeling (ΔLVEDD) was significantly enhanced compared to baseline (P=0.016). Additionally, a non-significant trend toward better improvement in LV function (ΔLVEF and ΔE/A) was observed in patients with MR amelioration.

Conclusion

LBBP, considered an optimal pacing technique for SSS or AVB patients, may substantially reduce MR and subsequently enhance LV remodeling and function compared to RVSP. This open, observational pilot study warrants confirmation through further investigations.Comparison between LBBP and RVSPKaplan-Meier curves for MR amelioration
Preexisting pulmonary hypertension impact on in-hospital outcomes of cardiac implantable electrical device implantation
Authors: Margolis G , Hafner O S , Kazatsker M , Roguin A , Leshem E
Published: October 2024

Background

Preexisting pulmonary hypertension (PH) is associated with unfavorable in-hospital outcomes in cardiac as well as non-cardiac surgeries and procedures. However, its impact on cardiac implantable electronic device (CIED) implantations is not established.

We investigated the extent of preexisting PH among patients undergoing CIED implantations and evaluated its effect on in-hospital outcomes.

Methods

Using the National Inpatient Sample (NIS) database, we identified patients who were hospitalized in the US between 2016-2019 and underwent CIED implantation with a preexisting diagnosis of PH. Patients with any CIED in-situ were excluded. Sociodemographic, clinical data, in-hospital procedures and outcomes as well as in-hospital mortality were collected. Multivariable logistic regression models were used to identify predictors of in-hospital complications.

Results

An estimated total of 718,980 patients underwent CIED implantation during the study period. Of them, 74,150 patients (10.3%) had preexisting PH diagnosis.

Compared with non-PH patients, PH patients were older, had higher Charlson Comorbidity Index, and more often implanted with implantable cardioverter defibrillators and cardiac resynchronization therapy devices.

Higher rate of total complications was observed in PH patients (14.5% versus 9.9%; P<0.001) driven mainly by respiratory complications as well as in-hospital mortality (2.3% versus 1.2%; P<0.001). Multivariable analyses confirmed PH as an independent predictor for respiratory complications, total complications and in-hospital mortality.

Conclusion

Preexisting PH in patients undergoing CIED implantation was associated with increased risk for respiratory complications as well as in-hospital mortality in a US nationwide, all-comer registry.
Integrated plasma proteomics and myocardial tissue transcriptomics reveal elevated fibrosis markers in arrhythmogenic cardiomyopathy patients
Authors: Akdis D A , Wilzeck V , Tan G , Costa S , Matter C , Brunckhorst C , Winnik S H , Akdis C A , Saguner A M , Duru F
Published: October 2024

Background

Arrhythmogenic cardiomyopathy (ACM) is characterized by myocardial fibrofatty replacement and ventricular arrhythmias, with potential progression to heart failure. This study aims to identify ACM-specific biomarkers for improved prognosis and possible treatment strategies.

Methods

RNA sequencing and transcriptome analyses were performed in cardiomyocytes of 10 ACM patients, 10 dilated cardiomyopathy patients and 10 healthy controls. Analyses were performed using liquid chromatography and mass spectrometry. Additionally, plasma protein expression was assessed in 38 ACM patients and 24 healthy controls using the Proximity Extension Assay (Olink®). A standardized bicycle exercise test was performed in 11 ACM patients and controls and blood was obtained before and after exercise.

Results

Myocardial tissue transcriptomics identified several upregulated molecules associated with extracellular matrix formation and immune response in ACM. Plasma protein sequencing revealed upregulation of proteins involved in metabolic pathways, inflammation, and fibrosis. Integration of these analyses identified key soluble profibrotic markers such as Fibulin-3, Endostatin and C-X-C motif chemokine 10 (CXCL10) in plasma of ACM patients. After exercise, Fibulin-3 levels increased in ACM patients compared to controls. These findings were further validated using enzyme-linked immunosorbent assay (ELISA).

Conclusion

This comprehensive analysis revealed distinct proteomic and transcriptomic signatures in ACM patients' plasma and cardiomyocytes. The integrative analysis identified several upregulated profibrotic markers in ACM. Our Findings may advance diagnostic and prognostic strategies and offer potential therapeutic targets.
Performance of the 2020 ACC/AHA and 2023 ESC risk stratification scales for primary prevention of sudden cardiac death in a Latin American population with hypertrophic cardiomyopathy
Authors: Casillas Munoz J P , Contreras Castillo P L , Nava Townsend S , Sanchez Contreras C A , Bazbaz Mizrahi A , Manzanarez Barrera J A , Marquez Murillo M F
Published: October 2024

Background

Identifying patients with hypertrophic cardiomyopathy (HCM) who are at high risk of sudden cardiac death (SCD) is essential for managing this condition. The American Heart Association/American College of Cardiology (AHA/ACC) and European Society of Cardiology (ESC) guidelines help assess and stratify the risk of determining which patients would benefit from primary prevention with an implantable cardioverter-defibrillator (ICD).

Objective

The study aims to evaluate the performance of the 2020 AHA/ACC and 2023 ESC risk stratification scales (AHA/ACC-rss; ESC-rss) for the primary prevention of SCD in Latin-American patients diagnosed with HCM.

Methods

A retrospective cohort of HCM from a single-center was analyzed. The inclusion criteria were individuals aged 16 years or older, without a history of SCD, and who had not undergone any treatment such as myomectomy or septal ablation with alcohol (Figure 1). The primary outcome was the identification of SCD or an equivalent event (successful resuscitation after cardiac arrest or appropriate therapy from the ICD).

Results

One hundred twenty patients were included (mean age 46.2 years old) and the mean follow-up duration was 61.1 months. From the total sample, 10 patients (8.3%) experienced an equivalent SCD event; 7 patients (5.8%) were ICD-protected and 3 (2.5%) required external defibrillation. The ESC-rss showed a greater area under the ROC curve (AUC, 0.79; 95% CI 0.62-0.94 vs AUC, 0.63; 95% CI 0.49-0.78) and specificity (85%; 95% CI 63-92 vs 51%; 95% CI 37.3-64.5). Sensitivity was similar between both scales (AHA/ACC-rss: 77%; 95% CI 50-100 vs ESC-rss: 73%; 95% CI 43-100). Remarkably, 2.5% of the patients who experienced an equivalent of SCD were incorrectly identified as low-risk individuals by either the AHA/ACC-rss, ESC-rss, or both (Table 1).

Conclusion

The SCD risk stratification recommended by the ESC-rss demonstrated a more effective identification of Latin American patients with HCM for ICD placement because the area under the curve was more significant than those of the AHA/ACC-rss. This single-center study highlights the need for a multicenter prospective study in Latin America.
Machine-learning models to predict the risk of recurrent VT following catheter ablation in patients with structural heart disease
Authors: Futela P , Behera G , Woelber T , Prasitlumkum N , Amin H , Arunachalam Karikalan S , Heybati K , Pradeep A , Kapa S , Deshmukh A J , Kowlgi G N
Published: October 2024

Background

Ventricular tachycardia (VT) is a life-threatening arrhythmia that can complicate structural heart disease. While catheter ablation is effective in treating this condition, the recurrence of VT after the procedure continues to be a concern. Consequently, there is a need for a reliable system to evaluate the likelihood of arrhythmia recurrence following an ablation.

Objective

To predict recurrence or repeat ablation after a VT catheter ablation procedure using machine learning (ML) models.

Methods

We conducted a single-center, retrospective study of all patients undergoing catheter ablation for scar-related VT between 2012 and 2022. Data collected included demographics, comorbidities, medications, relevant laboratory abnormalities, electrocardiograms, echocardiograms, detailed procedural characteristics, and outcomes. Python version 3.8.5 for exploratory data analysis (EDA) and visualization. Using six different ML models from the training set (90:10 split), we used 34 variables to predict the primary outcome, including VT recurrence or repeat catheter ablation. The accuracy of these models was compared using ROC curves based on their performance on the test set.

Results

Out of 508 VT ablation procedures, 261 experienced a recurrence. Support Vector Classifier (SVM) performed the best, having an AUC of 0.73, followed by logistic regression at 0.69 (Figure A). SVM yielded sensitivity, specificity, positive and negative predictive values of 0.73, 0.73, 0.79, and 0.67, respectively. The F1 score was 0.70. Among the factors with the highest feature importance in the model, the most influential variable was the proceduralist’s experience level, followed by QRS width at baseline, LVEF, and patient’s age (Figure B).

Conclusion

Our model can predict recurrent VT after ablation with reasonable accuracy, outperforming the existing clinical risk scores significantly. Larger training sample sizes will help achieve more robust ML models and improve predictive accuracy further.Figure A: ROC curve depicting the AUROCB. Feature importance graph
Outcomes of ventricular tachycardia ablation with intracardiac echocardiography-a retrospective cohort study of the national inpatient sample
Authors: Raj K , Singh Dhaliwal J , T Han F , S Hoffmayer K , Ho G , Raissi F , K Feld G , E Krummen D , C Hsu J
Published: October 2024

Background

Intracardiac echocardiography (ICE) is being increasingly used in VT ablation. Sparse literature indicates that ICE reduces repeat VT ablation and VT-related admissions (1).

Objective

To determine if ICE reduced procedural complications, mortality, length of stay, and hospitalization costs in VT ablation.

Methods

Utilizing the National Inpatient Sample (NIS) of the years 2016 to 2020, we compared the differences between patients who had VT ablation with and without ICE. We used multivariable logistic and linear regression models as appropriate to determine if ICE was associated with improved outcomes as defined above.

Results

We included 15,480 hospitalizations (95% CI 14,513-16,446) with VT ablations. ICE was used in 1815 (11.7%) of the patients. The mortality rate was 2.2%(95% CI 1.1-4.3) in the ICE group and 3.2% (95% CI 2.6-3.9) in the non-ICE group, and composite complications rate was 18.4% (95% CI 14.7-22.7) in the ICE group and 19.2% (17.7-20.8) in the non-ICE group. On univariate and multivariate analysis, ICE was not associated with a decrease in mortality, composite complications, or hospitalization charges but with a reduction in length of stay (Tables 1 and 2). ICE was associated with sepsis on univariate analysis but not on multivariate analysis (aOR 0.51, 95% CI 0.26-1.00, P=0.051)

Conclusion

Our study demonstrates that ICE was not associated with a reduction in mortality or complications in VT ablation but was associated with a slightly shorter length of stay. Although our observational study did not demonstrate a major benefit with ICE, given the multiple advantages of ICE in VT ablations, such as real-time recognition of myocardial substrate, identification of anatomical structures to guide ablation, and prompt recognition of intra-procedural complications, we recommend randomized controlled studies to evaluate the efficacy of ICE(2). Our study is limited by its retrospective nature and reliance on ICD codes for data extraction.
Nationwide trends in utilization and safety of ventricular arrythmia ablation in patients with hypertrophic cardiomyopathy
Authors: John K , Chee J , Chalhoub F , Infeld M , Homoud M , Ruskin J , Heist K , Udelson J , Madias C , Rozen G
Published: October 2024

Background

Catheter ablation for ventricular arrhythmias, including ventricular tachycardia (VT) and premature ventricular complexes (PVC) is increasingly utilized across the nation, while data on its safety in Hypertrophic Cardiomyopathy (HCM) patients is sparse.

Purpose

To analyze the nationwide trends in utilization and complications of inpatient ventricular arrhythmia ablations in patients with HCM.

Methods

This study is a retrospective analysis of hospitalizations, in HCM patients 18 years of age and older, who underwent an inpatient VA ablation in the U.S., between 2016 and 2020. We drew data from the National Inpatient Sample (NIS) database. Patients without HCM undergoing the CA for VA were used as controls. Baseline sociodemographic and clinical data, procedural complications, mortality and length of stay were analyzed. Multivariable analysis was performed to identify independent predictors of procedural complications.

Results

Among a weighted total of 2880 patients hospitalized between 2016 and 2020, who underwent VA ablations, the median age was 67 years (IQR 56-74), 60% were male, and 73% were white. The HCM group had similar age distribution but more women (64.5% vs 33.6%, p<0.001) and more African Americans (13.2% vs. 7.3%, p=0.03). The non-HCM cohort had significantly higher rates of prior myocardial infarction (22% vs 12.4%, p=0.026), ischemic cardiomyopathy (30.1% vs 0.8%, p<0.001), heart failure (70.5% vs 39.7%, p<0.001), and peripheral vascular disease (PVD, 42.9% vs 18.2%, p<0.001). This was reflected in higher Deyo Comorbidity Index in the non-HCM cohort (score of ≥ 2 in 66.6% vs 43%, p<0.001). Overall, the real-world peri-procedural complication rate in the entire cohort was 15.3%, including 6.4% hemorrhagic, 4.5% pericardial, and 2.3% vascular complications. There was a trend for lower complication rate in the HCM group (9.9% vs. 16.7%, p = 0.08). The in-hospital mortality didn’t defer (1.7% vs. 4.2%, p=0.28) and the length of stay was shorter in the HCM group (3.5 vs. 6.4 days, p < 0.001). Multivariable logistic regression analysis showed obesity (OR 2.06; 95%CI: 1.59 - 2.67; p<0.001) and PVD (OR 2.19; 95%CI: 1.34-3.53; p=0.001) to be independent predictors of complications while HCM was not (OR 0.76, 95% CI 0.51-1.14, p = 0.195).

Conclusion

Real-world data from a nationwide inpatient database shows comparable safety for VA ablation in HCM patients with similar mortality and lower length of stay, compared to non-HCM patients.
Safety profile, electrical performances and clinical outcomes of a novel leadless pacemaker; first results from real-world clinical practice in Saudi Arabia
Authors: Sweidan R S , Bokhari F B , Chami A C , Grammatico A G , Al-Samadi F A
Published: October 2024

Introduction

Leadless pacemakers (LP) are emerging as an effective and safe alternative to transvenous pacemakers to reduce lead-related and pocket-related complications and to improve patient experience. A new LP system, the Aveir VR, has been approved in 2022 for US and other countries, and in 2023 for Europe, and features innovative characteristics such as the active fixation helix mechanism and the possibility to measure sensing/pacing parameters before LP deployment.

Purpose

Evaluate safety, electrical performances and clinical outcomes associated with the first Aveir VR LP implants in 2 Hospitals in Saudi Arabia.

Methods

We performed a prospective evaluation of all-comer patients who received Aveir VR LP. Decision for LP implant was based on conditions such as cardiac pacing indication, lack of upper extremity venous access, risk of device infection, and life expectancy, and using shared decision-making. Clinical and electrical data were collected at implant and at 1st and 6th month visits.

Results

A total of 54 patients (25 female, mean age 69 years) were included between December 2022 and October 2023. Pacemaker implant indication was AV block in 25 (46%) patients, sinus node disease in 19 (35%) patients, atrial fibrillation and slow ventricular response in 9 (17%) patients and left bundle branch block in 1 (2%) patient. Implant was successful in all attempted cases. Final device position was lower septum in 51/54 (94.4%) patients and mid-septum in 3/54 (5.6%) patients. Mean procedure time was 48±22 minutes and showed a decreasing trend as a function of operator experience with a mean of 55, 50 and 36 minutes in the first, second and third group of consecutive implants, respectively. Mean fluoroscopic time was 11±8 minutes and showed a decreasing trend as a function of operator experience with a mean of 13, 13 and 6 minutes in the first, second and third group of consecutive implants, respectively. Final device position was achieved at first attempt in 42/54 (77.8%) cases and at first or second attempt in 51/54 (94.4%) cases. At implant mean R wave sensing was 7.6±3.7 mV, mean impedance was 724±335 Ohm, mean threshold was 1.0±0.6 V at 0.4 ms. During implant there was one patient with pericardial effusion treated with pericardiocentesis. In a mean follow-up of 73 days there were no procedure-related or device-related complications, electrical parameters showed acceptable values, and all implanted devices performed as expected. Median longevity, estimated at last follow-up visit, was 19 years (interquartile range: 12-20 years).

Conclusion

First real-world cases of use of a novel leadless pacemaker in Saudi Arabia show optimal feasibility and good safety profile and electrical performances. Procedure and fluoroscopic times were acceptable and decreased as a function of operator experience. Longevity estimations predict very long service life-times.
Long-term follow-up of single-chamber atrial pacing - system upgrade and wenckebach block point behavior: potential implications for leadless AAI pacing?
Authors: Arnet R , Badertscher P , Isenegger C , Minder J , Jordan F , Salis M , Spreen D , Knecht S , Krisai P , Osswald S , Sticherling C , Schaer B , Kuehne M
Published: October 2024

Introduction

Until recently leadless pacemakers (PM) did not support atrial pacing. A novel dual chamber leadless PM system now provides treatment option for a wide range of indications. Single-chamber atrial stimulation (AAI) for the treatment of symptomatic sick sinus syndrome (SSS) is scarcely used due to concerns about the potential development of atrioventricular block (AVB) and development of paroxysmal atrial fibrillation (AF). Long-term follow-up data of AAI-PM is however scarce. Little is known about the role of serial Wenckebach block point (WBP) measurements in AAI-PM patients for risk stratification.

Purpose

To assess the incidence of dual chamber upgrade of patients treated with AAI-PM for SSS during long-term follow-up and to investigate the role of serial WBP measurements for risk stratification.

Methods

Prospectively enrolled patients undergoing implantation of an AAI-PM between October 2002 and December 2023. WBP was measured at implantation and serially during follow up.

Results

We included a total of 178 patients, of which 58% were female and the median age at implantation was 78 [IQR 71 – 83] years. The median follow-up duration was 6.5 [IQR 2.0 – 9.7] years. 24 patients (13.5%) received a system upgrade to DDD including 3 patients (1.7%) with a mode change to ventricular pacing only (VVI). Adjusted for years of follow-up the upgrade rate was 2.1% per year. Median time to system upgrade was 5.2 [IQR 1.6 – 8.7] years. Reasons for system upgrade were high-degree AVB (38%), low WBP (17%), atrial arrhythmias (33%), unclear syncope (8%) and infection (4%). Median WBP at implantation was 130 [120 – 140] bpm, showing a significant decline over time in the upgrade-group with 105 [95 – 130] bpm compared to the rest of the cohort with 130 [120-130] bpm (p = 0.009). A decline in WBP >20 bpm was found in 17.9% patients and a decline of 10-20 bpm in 33.7% of patients. New-onset atrial arrythmias were found in 36 patients (20%), 29% in the upgrade group and 19% in the rest of the cohort (p = 0.3). Neither age at implantation, sex, WBP at implantation, nor atrial arrhythmia prior to implantation were predictive for the need of a future system upgrade.

Conclusion

In this cohort of patients undergoing AAI-PM implantation for SSS, a system upgrade was required in 2% per year. The WBP remained stable in 48% of patients. Therefore, AAI-PM due to SSS emerges as a judicious and secure therapeutic modality, warranting increased consideration in the light of new treatment options for leadless pacing.
Pacing sensation with a second generation intercostal extravascular ICD lead
Authors: Burke M C , Doshi S , Ebner A , Husby M , Marcovecchio A , Sanghera R , Scheck D , O'connor M , Chen S , Knops R E
Published: October 2024

Background/Introduction

An investigational intercostal extravascular ICD lead (EV-ICD Lead) has been developed to provide antitachycardia pacing and shock treatment of ventricular tachyarrhythmias when connected to a commercially available ICD pulse generator. Unlike other available extravascular ICD systems that achieve pacing with ring electrodes which transmit undirected current to cardiac and non-cardiac tissue alike, the intercostal EV-ICD Lead uses button-shaped electrodes backed by an insulative paddle to direct current toward excitable myocytes while minimizing undesired excitation of the adjacent tissues.

Purpose

The purpose of this analysis was to evaluate pacing sensation with the intercostal EV-ICD Lead connected to a commercially-available ICD pulse generator programmed to the maximum voltage output and pulse width settings.

Methods

In the STEP ICD Study (n=20), pacing sensation was evaluated at the pre-discharge visit while pacing at the maximum programmable voltage output (7.5 or 8.0 V, depending on manufacturer) and pulse width (1.5 or 2.0 ms). Sensation was reported by the patient as one of four choices: No Sensation, Sensation Only, Tolerable Pain or Intolerable Pain.

Results

Pacing sensation was assessed in 18 of 20 patients. One (1) patient did not undergo a pacing evaluation due to atrial fibrillation with rapid ventricular response. Responses were as follows: No Sensation in 4 (22%) patients, Sensation Only in 10 (56%) patients, Tolerable Pain in 3 (17%) and Intolerable Pain in 1 (6%). In no patient was the pain so severe that pacing capture threshold testing could not be completed. Of note, the single report of intolerable pain was only reported in the sitting posture. When tested supine, the patient reported sensation only.

Conclusion(s)

The design of the investigational intercostal EV-ICD Lead, with button-shaped electrodes backed by an insulative paddle, produced low levels of patient sensation at maximum output and pulse width. These sensation levels represent an improvement over designs that employ ring electrodes and indicate that antitachycardia pacing will be well tolerated with the novel EV-ICD Lead. These results corroborate the predictions about patient discomfort from in silico models.
Predictive value of a positive pocket swab for the occurrence of device infection in implantable cardioverter defibrillator patients undergoing generator replacement or lead revision
Authors: Kleemann T , Mousavi S B , Kouraki K , Strauss M , Mohammad O , Wenz A , Weisse U , Werling C , Sack F , Zahn R
Published: October 2024

Introduction

Bacterial colonization of generator pockets in implantable cardioverter defibrillator (ICD) patients plays a key role in the development of device infection after revision surgery. Pocket swabs taken at revision may be useful for predicting device infection, but their prognostic value is not precisely known. Aim of the study was to evaluate the predictive value of positive pocket swabs for cardiac device infection in ICD patients undergoing revision surgery.

Methods

A total of 646 consecutive ICD patients from a prospective single-centre ICD-registry who underwent elective device replacement, system upgrade or lead revision between 2014 and 6/2023 were analyzed. Independent predictors for device infection were evaluated by a Cox regression analysis adjusting for age, gender, EF, insulin dependent diabetes, anticoagulation, multiple leads, revision surgery and the PADIT score.

Results

Positive pocket swabs were obtained in 12% of patients. The baseline characteristics of ICD patients with positive versus negative pocket swabs were similar (Table 1). With an average follow-up of 3 years, the infection rate in patients with positive pocket swabs was around 5 times higher than in patients with negative swabs (19% versus 4%, p < 0.001). In a Cox regression analysis, a positive pocket swab was the strongest independent predictor for device infection during follow-up (hazard ratio 4.26, 95% confidence interval 2.15 – 8.45, Table 2).

Conclusion

A positive swab from ICD-pockets in patients undergoing generator replacement or lead revision is an independent predictor of device infection during follow-up. These results support the routine collection of pocket swabs from patients undergoing revision surgery.Table 1Table 2
Genetic and phenotypic architecture of biventricular trabeculation
Authors: Mcgurk K , Ware J S , O'regan D P
Published: October 2024

Introduction

Cardiac trabeculae form a network of muscular strands that line the inner surfaces of the heart, and their development involves molecular pathways that regulate structural complexity. Excessive or hypertrabeculation occurs as part of normal variation in apparently healthy individuals, as an adaptation to altered loading conditions, and is observed in patients with cardiomyopathies (CMs) and heart failure (HF).

Purpose

In adults, trabeculation is not a prognostic factor independent of the underlying myocardial disease but may play a role in the natural history of ventricular remodelling. We sought to (i) understand the genetic and non-genetic determinants of trabeculation, (ii) understand its role in the causality of disease, and (iii) evaluate trabeculation as a biomarker for diagnosis and stratification.

Methods

We report genes with a burden of rare variants and novel common variant associations across the allele frequency spectrum for biventricular trabecular morphology in 47,803 participants of the UK Biobank using fractal dimension analysis of cardiac imaging (Figure 1). We assessed environmental modifiers of trabecular morphology, correlation with cardiac traits, phenome-wide association studies, and the relationship with the progression of CMs and HF.

Results

We identified a burden of trabeculation-associated rare variants in genes that regulate myocardial contractility and cardiac development and GWAS identified novel loci near genes implicated in CMs, conduction traits, and signalling pathways that define the early development of trabeculation. For example, we identified 56 genes with a burden of rare variants and 68 novel loci from GWAS (e.g., CASQ2, CACNA1C, MYBPC3, MYH7, NKX2-5, NOTCH1, TBX20) for the left ventricle.

The strongest imaging relationships with trabeculation were with measures of volume and strain. Modifiers of trabeculation included African ancestry, alcohol intake, and physical activity. Carriers of CM-associated pathogenic variants had increased trabeculation. Of participants with CM reported after imaging, 25% had hypertrabeculation on imaging and hypertrabeculation was a risk factor for a subsequent diagnosis of HF (HR=1.3), mitral valve disorders (HR=1.4), bundle branch block (HR=1.2). Comparisons of biventricular trabeculation showed similarities in trabeculation across the ventricles in CM. Reduced right ventricular trabeculation and end-diastolic volume associated with Type-2 diabetes.

Conclusions

These data provide new insights into the mechanisms that regulate structural complexity in the heart. Changes in trabeculation may occur early in the pathogenesis of heart disease, can be modified by genes regulating pathways outside the sarcomere, and causality depends on the underlying cardiomyopathic substrate. Trabeculation progresses with cardiovascular disease, is a useful marker of remodelling, and identifies novel genetic modifiers of ventricular complexity.Figure 1
Primary inflammatory disease in heart failure with preserved ejection fraction
Authors: Tada A , Doi S , Harada T , Ibe T , Jwan N , Amdahl M , Reddy Y , Borlaug B
Published: October 2024

Background

Inflammation plays a fundamental role in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of underlying systemic inflammatory diseases represented by rheumatoid arthritis.

Purpose

This study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and primary inflammatory diseases.

Methods

Consecutive patients undergoing hemodynamic exercise testing with concurrent expiratory gas analysis to evaluate dyspnea of unknown cause were identified. HFpEF was defined as left ventricular ejection fraction ≥50% and pulmonary capillary wedge pressure ≥15 mmHg (rest) or ≥25 mmHg (exercise). Patients with HFpEF were divided into groups with and without primary inflammatory diseases. Patients without inflammatory disease were divided into tertiles according to the value of C-reactive protein (CRP).

Results

Of 982 consecutively evaluated patients with HFpEF diagnosed (577 female, mean age 68 years), 79 (8%) had primary inflammatory disease. In multivariable logistic regression, female sex (OR 1.88; 95% CI 1.01-3.52), higher resting heart rate (OR 1.18; 95% CI 1.08-1.30), lower hemoglobin level (OR 0.84; 95% CI 0.70-0.99), absence of history of atrial fibrillation (OR 0.45; 95% CI 0.24-0.86) and absence of epicardial coronary artery disease (OR 0.45; 95% CI 0.22-0.93) were independently associated with inflammatory disease. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with inflammatory disease, reflected by lower arterial-venous oxygen content difference (Ca-vO2) at rest (4.2±0.7 mL/dL vs 4.6±1.0 mL/dL, P<.001) and during exercise (9.3±2.2 mL/dL vs 10.4±2.2 mL/dL, P<.001) (Figure 1A), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCO2 slope) was also more impaired (38.0±7.9 vs 36.2±7.3, P=.035). The HFpEF patients without inflammatory disease falling in the highest tertile of CRP) displayed lower Ca-vO2 during exercise, more closely resembling peripheral deficits observed in those with inflammatory disease (Figure 1B). During a median follow-up of 3.0 years, the composite outcome of all-cause deaths and HF hospitalization occurred in 127 patients (14%). Patients with HFpEF and inflammatory disease showed a higher incidence of composite outcome than those without (log-rank P=.030; Figure 2). Patients with inflammatory disease had higher risk of composite outcome compared to those without in adjusted analyses (HR 1.93; 95% CI 1.15-3.23), which was primarily attributable to higher risk of HF hospitalization (HR 2.85; 95% CI 1.08-7.52).

Conclusion

Patients with HFpEF and primary inflammatory disease have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared to those without.
Prognostic value of hemodynamically significant secondary tricuspid regurgitation in patients hospitalised for heart failure with preserved ejection fraction
Authors: Decotto S , Fernandez Villar G , Rossi E , Lucas L , Perez De Arenaza D , Belziti C , Pizarro R
Published: October 2024

Introduction

Heart Failure with preserved ejection fraction (HFpEF) is a significant clinical concern, characterized by a rising prevalence and substantial morbidity. Despite the frequent presence of secondary tricuspid regurgitation (TR) in this population, its prognostic implications remain unknown.

Purpose

The aim of this study is to assess the rate of the composite of mortality and heart failure readmissions by considering the presence of hemodynamically significant secondary TR in patients hospitalised for HFpEF.

Methods

Prospective observational cohort study. Patients admitted for acute HFpEF (ejection fraction > 50%) between September 2019 to December 2022 were included. Patients with primary TR, pacemaker, moderate-severe left valve disease, end-stage renal failure (creatinine clearance < 30 ml/min/BSA) and recent myocardial infarction were excluded. TR was considered significant if rated as moderate or higher, following established semi-quantitative and quantitative criteria in current guidelines. Patients were followed-up for one year to assess the incidence of the composite primary outcome of death and heart failure readmission.

Results

A total of 110 patients were included. Median age was 85 [78-89] years, 64% were female. The mean left ventricle ejection fraction was 57% (+/-5%). Significant TR was observed in 44.5% (n=49) of cases. Patients with significant TR had higher NT-ProBnp values (4555 [2620-7025] pg/mL vs 2400 [1300-5494] pg/mL; P = 0.01), and worse echocardiographic parameters of right heart size and function compared to those without significant TR (TABLE). The incidence of the composite outcome was higher in patients with significant TR compared to patients without significant TR (P = 0.01, LogRank test) (FIGURE). In a Cox regression multivariate analysis including age and sex, significant TR was independently associated with the incidence of the primary outcome (HR 1.86; CI 1.10 - 3.13; P = 0.006).

Conclusion

In patients hospitalised for HFpEF, significant TR was independently associated with a higher incidence of death and heart failure readmission at one year-follow-up. Further research is needed in this group, particularly to explore novel risk stratification and therapeutic approaches.Kaplan-Meier curveTable