bluuebunny/crossref_metadata_2025 huggingface dataset:
Risks of incident genitourinary malignancies in anticoagulated atrial fibrillation patients experiencing hematuria
Authors: Chao T , Kuo L , Lip G Y H
Published: October 2024

Background

When managing oral anticoagulant (OAC)-related bleeding in patients with atrial fibrillation (AF), the possibility of occult malignancies should be kept in mind, as suggested by guidelines. In this study, we aimed to investigate the incidence of genitourinary (GU) trat cancer in anticoagulated AF patients experiencing hematuria. Also, we aimed to report the prevalence of other causes of hematuria beside malignancy.

Methods

We conducted a nationwide, retrospective cohort study in Taiwan. A total of 19,974 AF patients aged ≥ 20 years on OAC treatment (warfarin 9232, non-vitamin K antagonist OACs [NOACs] 10,742) experiencing hematuria were enrolled. Risk of newly diagnosed GU malignancy within one year after hematuria was reported and compared between patients receiving warfarin and NOACs.

Results

A total of 738 patients (3.99%) were diagnosed to have GU tract cancers within 1 year after OAC-related hematuria, with prostate cancer (52.30%) being as the commonest subtype, followed by bladder cancer (31.71%) and kidney/ureter/urethra in origin (15.99%)(Figure 1). The risk of GU tract cancer was higher for warfarin compared to NOAC users (4.10% versus 3.89%; odds ratio 1.169, p = 0.041)(Figure 1). For patients without diagnosed GU tract cancers, urinary tract infection (42.3%) was the leading cause of hematuria followed by benign prostate hyperplasia (37.6%), GU tract stone (16.7) and cystitis (9.2%)(Figure 2). Overall, 27.5% of patients whose causes of hematuria could not be identified (Figure 2).

Conclusions

Incident GU cancers were diagnosed in 1 of 25 AF patients at 1 year after OAC-related hematuria. Detailed examinations for occult GU cancers and other etiologies are necessary.
Implications of renal function on adverse clinical events in patients with atrial fibrillation: a comparative analysis of VKA and NOAC therapy - Insights from the GLORIA-AF Registry Phase III
Authors: Liu Y , Chen Y , Lam S H M , Huang B , Chao T F , Olshansky B , Lip G Y H
Published: October 2024

Background

Renal function, as assessed by creatinine clearance (CrCl), plays a crucial role in determining the efficacy and safety of oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF).

Purpose

To investigate the relationships between CrCl and the risk of clinical adverse events in patients with AF receiving OAC therapy, comparing the safety profiles of vitamin K antagonists (VKA) and non-vitamin K antagonist oral anticoagulants (NOACs).

Methods

Anticoagulated AF patients from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry Phase III were studied. CrCl was calculated for renal function, according to Cockcroft-Gault equation. Restricted cubic spline (RCS) were used to explore the nonlinear association between adverse end events and CrCl, comparing VKA and NOAC therapy. Cox regression models were used to analysis the associations between adverse end events and OAC therapy in patients with different CrCl levels, adjusted by clinical features and previous disease. Patients were followed up for the composite outcome (all-cause death, thromboembolism and major bleeding), all-cause death, cardiovascular disease (CVD), major bleeding, myocardial infarction (MI) and stroke.

Results

In 10,594 AF patients (mean age 70.35 ± 9.92 years; 55% male; 73% on NOAC), RCS analysis revealed decreased risks of all cause death, composite outcomes and CVD with increasing CrCl in patients with CrCl < 80 mL/min.

Multivariate Cox models indicated that NOAC therapy associated with lower risk of all cause death (HR 0.68, 95% CI 0.58-0.78), composite outcomes (HR 0.77, 95% CI 0.68-0.86), CVD (HR 0.7, 95% CI 0.56-0.87), major bleeding (HR 0.74, 95% CI 0.61-0.91) in AF patients. For CrCl > 95 mL/min, a lower risk of all cause death (HR 0.56, 95% CI 0.38-0.82), composite outcomes (HR 0.68, 95% CI 0.51-0.91) and major bleeding (HR 0.54, 95% CI 0.35-0.85) were associated with NOAC therapy, vs. VKA.

For CrCl < 30 mL/min, a lower risk of all cause death (HR 0.47, 95% CI 0.28-0.81), composite outcomes (HR 0.56, 95% CI 0.35-0.89) and CVD (HR 0.43, 95% CI 0.20-0.90) were related to NOAC therapy. No significant difference in outcomes between VKA and NOAC were found in patients with moderate CrCl.

Conclusion

Increasing CrCl were associated with decreased risk of adverse clinical events, including all-cause death and CVD in anticoagulated AF patients. For patients with CrCl >= 95 and < 30, NOAC therapy, was associated with lower risks of adverse outcomes.Figure 1Figure 2
Switching from warfarin to a DOAC in frail elderly asian patients with atrial fibrillation: a nationwide population-based study
Authors: Go Y , Lee S , Choi E , Rha H , Jeong M , Yeo M , Choi J , Lee K , Ahn H , Kwon S , Kim B , Han K , Oh S , Lip G
Published: October 2024

Background

Recently, switching international normalized ratio guided warfarin management to a direct oral anticoagulant (DOAC) was associated with more bleeding complications than maintaining warfarin in frail elderly patients with atrial fibrillation (AF). However, there is a paucity of information on whether these results could be applied to Asian patients with AF, who are known to have relatively low time in therapeutic range (TTR) levels.

Purpose

To evaluate the safety and effectiveness of switching from warfarin to a DOAC in frail elderly Asian patients with AF.

Methods

Using a Korean health insurance database, we included patients with AF who were prescribed warfarin between January 2013 and August 2015 without significant bleeding or thromboembolic events during the window period, specifically those aged 75 or older with a Hospital Frailty Risk Score of 5 or more. Those who switched to DOACs during the window period were categorized as the DOAC group and those who continued with warfarin were categorized as the warfarin group. The primary outcome was defined as the composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB), and secondary outcomes were defined as thromboembolic events, all-cause death, the composite of MB, CRNMB and ischemic stroke (so-called net clinical outcome [NCO]). The propensity score weighting method was utilized to compare the two groups.

Results

A total of 12,162 patients were included (8,108 with maintaining warfarin, 4,054 with switching to a DOAC). Baseline characteristics were well-balanced after the inverse probability of treatment weighting (mean age, 80 years; men, 50%; and mean CHA₂DS₂-VASc score, 5.6). Compared with maintaining warfarin, switching to a DOAC was associated with significantly higher risks of the primary outcome (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.09-1.87, p=0.01), thromboembolic events (1.28, 1.01-1.62, p=0.039), all-cause death (1.38, 1.15-1.66, p<0.001) and the NCO (1.26, 1.01-1.58, p=0.04). (Figure A, Figure B), whereas there was no difference in the risk of intracerebral hemorrhage (0.90, 0.50-1.60, p=0.7157). When comparing each DOAC with maintaining warfarin, switching to rivaroxaban was associated with a higher risk of the composite of MB and CRNMB (1.91, 1.38-2.64, p<0.001) and thromboembolic events (1.40, 1.03-1.91, p=0.034) than maintaining warfarin.

Conclusion

In line with the non-Asian population, switching to a DOAC was associated with a significantly higher risk of MB or CRNMB, thromboembolic events, all-cause death and NCO compared with maintaining warfarin in frail elderly Asian patients with AF. Therefore, even in Asians, switching to a DOAC should be considered more cautiously in patients who are stably managed on warfarin.
Plasma apixaban levels and thrombin generation assay in patients with atrial fibrillation with dose reduction criteria of apixaban
Authors: Yeo M , Lee S R , Choi E K , Ahn H J , Kwon S , Oh S
Published: October 2024

Background

Off-label reduced-dose apixaban is commonly prescribed in patients with atrial fibrillation (AF). However, the pharmacokinetic data of apixaban according to the dosage and label is limited especially in those with dose reduction criteria of apixaban.

Purpose

We investigated the apixaban plasma concentration (PC) and thrombin generation assay (TGA) parameters across different apixaban dose settings.

Methods

We enrolled 398 non-valvular AF patients with more than single-dose reduction criteria of apixaban and divided them into three groups: (1) on-label standard dose (single dose-reduction criterion with standard-dose of apixaban 5mg twice daily, n=173); (2) off-label reduced-dose (single dose-reduction criterion with apixaban 2.5mg twice daily, n=61); and (3) on-label reduced-dose (two or more dose-reduction criteria with apixaban 2.5mg twice daily, n=164). Apixaban PC by anti-Xa assay and TGA parameters of these three groups were compared at the trough level.

Results

The on-label standard dose group showed a higher PC than the on-label reduced dose (124.7 vs. 80.3 ng/mL, p<0.001), and the on-label reduced dose exhibited a higher PC than the off-label reduced dose (80.3 vs. 53.2 ng/mL, p=0.031) (Figure). The TGA parameters displayed a similar pattern of differences, with the on-label standard dose group tends to show the least thrombogenic profiles (Figure). Lower creatinine clearance (CrCl), older age, and female sex were statistically significant predictors for a higher apixaban PC by multivariable regression model (p<0.001, p=0.043, and 0.023, respectively), and CrCl was the most influential variable to dichotomize apixaban PC in all three groups (Figure).

Conclusions

Off-label reduced-dose apixaban group exhibited significantly lower apixaban level than both on-label standard dose and on-label reduced-dose apixaban groups, suggesting the importance of adhering to current dose-reduction criteria for maintaining appropriate apixaban levels. Caution is particularly advised in off-label under-dosing for patients with high creatinine clearance. Further investigation into the impact of off-label under-dosing on clinical outcomes is essential to guide optimal therapeutic strategies.
Prognostic value of left atrial strain for outcome of catheter ablation in patients with atrial fibrillation and moderately enlarged left atrium
Authors: Kim M H , Cho I , Kim K , Kim D , Yu H T , Kim T H , Joung B , Lee M H , Pak H N
Published: October 2024

Background

Atrial fibrillation catheter ablation (AFCA) is an effective rhythm control method for patients with AF, but AF recurrence is higher in patients with a large left atrium (LA). We explored whether pre-procedural LA strain has incremental prognostic value for the long-term rhythm outcomes of AFCA in patients with AF and moderately enlarged LA size (45≤LA diameter<50mm).

Methods

We included 2,269 patients who underwent de novo AF catheter ablation (men 72.2%, 59.1[±10.7] years, paroxysmal AF 64.0%). We divided grouped into 5 mm increments and determined the appropriate cut-off of LA diameter (45mm) predicting the difference in long-term rhythm outcome by the log-likelihood values of multivariate Cox proportional hazard models. Patients with moderately enlarged LA size (45≤LA diameter<50mm, n=413) with borderline rhythm outcomes were used for analysis.

Results

In the cohort of 413 patients who underwent AFCA with moderately enlarged LA size, AF was recurred in 208 patients (43.7%) after AFCA. We determined the appropriate cut-off of LA strain (12.5) predicting the difference in long-term rhythm outcome by the log-likelihood values of multivariate Cox proportional hazard models. During 24 months [10-50] follow-up, patients with low LA strain (<12.5) were showed worsen rhythm outcome than high LA strain (Log-rank p<0.001). Patients with AF recurrence after AFCA were independently associated with low LA strain (HR 1.539 [1.130-2.094], p=0.006), and paroxysmal AF (OR 0.651 [0.469-0.905], p=0.011). Furthermore, the likelihood ratio test demonstrated a significant influence of adding LA strain by TTE (χ2 = 13.90 [P < 0.001]).

Conclusions

LA strain using baseline echocardiography has a predictive power for AF recurrence after AFCA in patients with moderately enlarged LA size (45≤LA diameter<50mm).
Impact of changes in proteinuria on the risk of atrial fibrillation in patients with diabetes mellitus: a nationwide population-based study
Authors: Rha H , Lee S R , Choi E K , Go Y H , Jeong M H , Choi J M , Lee K Y , Kwon S , Kim B , Han K D , Oh S , Lip G
Published: October 2024

Background

Diabetes mellitus (DM) is a well-known risk factor for atrial fibrillation (AF). Proteinuria is also considered as an independent predictor for AF. However, there is limited data on whether the changes in proteinuria severity can impact the risk of AF among patients with DM.

Purpose

We aimed to evaluate the association between changes in proteinuria over time detected using a urine dipstick test and the risk of AF among patients with DM.

Methods

A total of 1,605,495 patients with DM who underwent two biennial health checkups provided by the National Health Insurance Service (NHIS) between January 2013 and December 2016 were included. All patients had two consecutive urine dipstick tests during the checkups. We divided the study population into four groups based on their glomerular filtration rate (GFR): > 90 ml/min, 60-90 ml/min, < 60 ml/min, and those with end-stage renal disease (ESRD). We evaluated the association between the changes in proteinuria over time detected using a urine dipstick test and the risk of AF and their changes by GFR.

Results

During a median 4.0-year follow-up, AF occurred in 32,391 persons (5.22 per 1,000 person-years). Among 1,605,495 patients who underwent two consecutive urine dipstick tests, 1,453,116 (90.51%) patients had a negative proteinuria on both tests (negative or trace result on both urine dipstick tests), and 68,979 (4.3%) patients had an aggravated proteinuria (from negative to more than 1+ result on subsequent urine dipstick test). While 48,357 (3.01%) patients had a resolved proteinuria (from positive to negative results on subsequent tests) and 35,043 (2.18%) patients had a persistent proteinuria (positive result on both tests). Those with aggravated or resolved or persistent proteinuria showed an increased risk of AF (HR 1.39, 95% CI 1.33-1.46; HR 1.37, 95% CI 1.30-1.45; HR 1.95, 95% CI 1.85-2.06) compared with most subjects who showed subsequent negative results on proteinuria. This result was consistent within every GFR group. However, the tendency of increment of AF risk by changes in proteinuria was more prominent in lower GFR groups (Table). In subgroup analysis, there was no significant difference between male and female. However, the younger aged (< 65 years) group had a more prominent tendency of increased AF risk by changes in proteinuria.

Conclusion

Changes in proteinuria showed a significant association with the risk of AF in patients with DM. This tendency was prominent in patients with lower GFR. Therefore, careful monitoring of AF risk based on proteinuria changes could be beneficial for those with DM.
Automatic measurement of stimulation to maximum negative dv/dt in V5 and V6 leads to confirm left bundle capture for conduction system pacing
Authors: Musat D , Bhatt A , Paamand R , Leonard O , Firth K , Mittal S
Published: October 2024

Introduction

Left bundle area conduction system pacing is obtained when the ventricular pacing lead is implanted into the right ventricular septum and captures the left bundle branch, demonstrated by right bundle branch morphology in the lead V1 and short stimulation to R-wave peak time (SRWPT) in leads V5 or V6. Manual measurements are challenging and result in significant variability. Maximum negative dv/dt in leads V5 and V6, occurring immediate after maximal lateral wall depolarization, represents the ideal measurement of synchronicity of left ventricular depolarization, as suggested by the guidelines.

Objective

To test feasibility of automatic algorithm to measure the maximum negative dV/dt in comparison to manual SRWPT measurement in V5 and V6.

Method

Data was collected from 7 patients with confirmed left bundle branch capture. Three trained operators manually measured SRWPT in leads V5 and V6 (Figure A). An algorithm capable of automatically measuring stimulation to maximum dv/dt was retrospectively applied to the same measured beats. Variability and correlation of measurements was compared between manual and automatic using the Bartlett Test for equal variance.

Results

In total, 137 individual beats were measured in the 2 leads by three operators resulting in 822 manual measurements. The mean variability of SRWPT in V5 and V6 was 2.9 ± 0.7 msec and 3.1 ± 1.1 msec, respectively (inter-operator correlation of 0.83). In contrast the stimulation to max negative dv/ dt mean variability in V5 and V6 was 1.3 ± 0.4 msec and 1.2 ± 0.5 msec, respectively (P < 0.001). The comparison of variation in measurement between manual and automatic measures are shown in a box and whisker plot in figure 2.

Conclusion

Manual measurement of SRWPT can be challenging resulting in higher variability compared to an automatic algorithm measuring max negative dv/dt. This study demonstrates the feasibility of automatic interval measurement in conduction system pacing; however, further studies are required to validate the reliability of such tool.Fig 1.Example ECG interval measurement
High incidence of malignant arrhythmias and heart failure in patients with RBM20-associated cardiomyopathy: a multicenter cohort study and review of the literature
Authors: Tukker M , Te Rijdt W , Amin A S , Morris-Rosendahl D J , Hirsch A , Ben-Haim Y , Houweling A C , Varnava A , Behr E R , Hajdarpasic A , Von Der Thusen J , Michels M , De Boer R A , Van Slegtenhorst M A , Caliskan K
Published: October 2024

Background

Patients with RBM20 cardiomyopathy commonly experience malignant arrhythmias, sudden cardiac death (SCD), and progressive heart failure (HF).

Objective

The aim of this study is to investigate genotype-phenotype correlations, clinical outcomes and causes of death in patients with RBM20-associated cardiomyopathy in a multicenter cohort, combined with an overview of the current literature.

Methods

This international, multicenter cohort included all patients with cardiomyopathy who had a pathogenic (P) or likely pathogenic (LP) RBM20 variant. For survival and regression analysis, we matched a control group based on sex, age, and presence of left ventricular dysfunction. Additionally, we conducted a literature search on studies investigating RBM20-associated cardiomyopathy.

Results

Sixty-two patients (45% male) were included in the study, with a mean age of 42 ± 15 years at presentation. Of the LP/P RBM20 variants identified, 9 were novel. Eleven variants were truncating, while the remaining variants consisted of missense and splice-site variants. Patients with a truncating variant who developed HF were on average older at the time of diagnosis compared to patients with missense variants (mean age 62 ± 9 vs. 45 ± 14; p=0.01). After a median follow-up duration of 5.0 [1.0 – 10.5] years, 21 (34%) patients reached the composite endpoint of ventricular arrhythmias (VA), implantable cardioverter-defibrillator therapy, heart transplantation (HTx), left ventricular assist device (LVAD) implantation, or cardiovascular death. Of these, 19 (31%) patients experienced malignant VA (mean age 45 ± 15 years, 63% males). Males were at higher risk for the composite endpoint (log-rank p= 0.02), particularly for VA (log-rank p=0.007). The literature review analyzed 34 studies with a total of 678 patients, of whom 53% were male. In these studies, 123 (24%) patients experienced a VA, 58 (12%) underwent HTx or were treated with LVAD, and 52 (11%) died.

Conclusion

In this multicenter study the patients carrying a LP/P variant in RBM20 variants had a severe phenotype, with a high incidence of VA, particularly in males. Additionally, this study presents 9 novel DNA variants, of which 8 were truncating, and were mainly observed in older individuals. Finally, we report a lower mortality rate compared to the literature, possibly due to a higher number of heart transplantations performed in our patient cohort.Survival composite endpoint for sex
Refining risk stratification in hypertrophic cardiomyopathy: the role of late gadolinium enhancement and syncope in predicting adverse outcomes
Authors: Mann C , Dachs T M , Tosun R , Kronberger C , Beitzke D , Loewe C , Kammerlander A A , Hengstenberg C , Zelniker T A , Dalos D
Published: October 2024

Background

The presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (MRI) is recognized as a significant marker of myocardial fibrosis and a predictor of adverse outcomes in hypertrophic cardiomyopathy (HCM). Nevertheless, the specific quantity of LGE that correlates with poor outcomes is still under debate. Therefore, this study sought to assess the combined impact of LGE presence and a history of syncopal events and its association with clinical prognosis.

Methods

Between May 2018 and June 2023, a total of 230 HCM patients was prospectively enrolled at our Medical University, a tertiary referral center. The primary endpoint was a composite of new-onset ventricular tachycardia (VT), appropriate ICD therapy, and all-cause mortality.

Results

Median age of enrolled patients was 56 (IQR 44-64) years and 40% (n=94) were female. Median interventricular septal thickness (IVS) was 21 (IQR 18–25) mm and 43 % (n=84) had significant left ventricular outflow tract obstruction (LVOTO).

Over a median follow-up of 3.2 years, 30 patients (13%) met the composite endpoint. These patients had a significantly higher LGE quantity compared to the non-event group (1.1 % vs. % 9.0, P=0.012). An LGE threshold of 5.2% was identified as an optimal predictor of the composite endpoint, with an area under the curve of 0.72, which increased to 0.77 when including at least one syncopal event in medical history. LGE > 5.2% and/or syncope were independently associated with adverse outcomes after multivariable adjustment (Adj HR 7.26 [95%CI 2.54-20.72]).

Furthermore, NTproBNP and hsTnT were associated with the presence of LGE or syncope (OR for a 1-unit increase in standardized log-transformed biomarker NTproBNP 3.35 [95%CI 1.42-10.85]; hsTnT 3.48 [95%CI 1.48-10.24], respectively). Interestingly, typically used variables for risk stratification, such as age, IVS or LVOT were not significantly associated with these cardiac biomarkers.

Conclusion

An extent of LGE > 5.2% and the history of at least one syncope are associated with unfavorable clinical outcomes in HCM patients. These findings call for detailed MRI appraisal and suggest adopting a holistic approach to accurately identify high-risk patients.
The association between exercise-induced ventricular premature contractions and long-term mortality in patients without coronary artery disease
Authors: Pay L , Tezen O T , Cetin T C , Eren S E , Oz M O , Coskun C C , Yumurtas A C Y , Karabacak C K , Yeniturk B Y , Cinar T C , Hayiroglu M I H
Published: October 2024

Background/Introduction

The treadmill exercise test is widely used clinical test to determine cardiovascular risk and mortality, regardless of clinical risk factors (1). ST-segment changes detected in the exercise test are shown to predict myocardial ischemia (2) and premature ventricular complexes (PVCs) are frequently observed during exercise stress testing (3). Exercise-related PVC is observed in 14% to 23% of healthy individuals without significant heart disease (4,5). The literature on the role of PVCs observed during treadmill exercise testing in predicting prognosis is controversial.

Purpose

Therefore, we aimed to evaluate the clinical results of PVCs seen during exercise testing in patients who had been diagnosed with non-obstructive coronary artery disease after coronary angiography.

Methods

The study population consisted of 1624 consecutive patients who were considered high risk according to the Duke treadmill risk score and had no significant stenosis on coronary angiogram from January 2016 to April 2021. Patients with previous history of coronary revascularization, previous myocardial infraction, heart failure, moderate or severe heart valve disease, congenital heart disease, cardiomyopathy, bundle branch block, and left ventricular hypertrophy were excluded from the study. The primary endpoints of the study were long-term all-cause mortality of patients who had PVCs during the exercise test or during the resting phase.

Results

The long-term mortality was observed in 53 patients out of 1624 patients in the mean follow-up of 47 months. PVCs was observed in 293 (18.7%) patients without long-term mortality, while PVCs was observed in 24 (45.3%) patients with long-term mortality (p<0.001). The model adjusted for all covariates showed that the presence of PVCs in the recovery phase (p<0.007, HR (95% CI) 2.244 (1.244 – 4.047)) and advanced age (p<0.001, HR (95% CI) 1.194 (1.143 – 1.247)) were associated with long-term all-cause mortality (Figure 1). Considering Kaplan-Meier curve, individuals with PVCs in recovery had significantly higher risk of long-term mortality compared with those with without PVCs (log-rank statistic: 22.47, p<0.001) (Figure 2).

Conclusion(s)

The study highlights that PVCs monitored in the recovery phase of the treadmill exercise test were associated with long -term mortality in patients without structural heart disease and coronary artery disease.Figure 2Figure 1
Novel electric predictors of lethal arrhythmic event in patients with hypertrophic cardiomyopathy
Authors: Choi J I , Jeong J H , Kook H D , Lee H S , Choi Y Y , Kim S R , Cho D H , Kim Y G , Kim M N , Shim J , Park S M , Kim Y H
Published: October 2024

Background

Little is known regarding the association between electrical markers and lethal arrhythmic events (LAE) in patients with hypertrophic cardiomyopathy (HCM). This study aimed to identify the electrical predictors of LAE in adult patients with HCM.

Methods

This study was a retrospective analysis of patients with HCM at a single center from 1998 to 2021. LAE was defined as a composite outcome of (1) sustained ventricular arrhythmia, (2) aborted sudden cardiac death (SCD), (3) implantable cardioverter defibrillator (ICD) implantation, and (4) appropriate ICD shock. A 12-lead electrocardiography was performed at the time of diagnosis.

Results

A total of 611 patients with HCM were analyzed, and 48 (7.8%) experienced LAE. Patients who experienced LAE were diagnosed at a younger age and more frequently had history of ventricular arrhythmia, new-onset atrial fibrillation (AF) or non-sustained ventricular tachycardia. New-onset AF, an increase in the QTc interval, and the absence of massive LVH were associated with LAE risk. In addition to conventional markers of HCM Risk-SCD, consideration of the QTc interval and massive LVH on electrocardiography improved the prediction of LAE (area under curve 0.682 to 0.740). Further inclusion of new-onset AF, history of ventricular arrhythmia, HCM type, and left ventricular mass index improved the predictability to 0.867.

Conclusion

An increase in the QTc interval, the absence of a massive LVH pattern on electrocardiography (ECG), and new-onset AF were independently associated with an increased risk of LAE. Comprehensive stratification using electrical markers improves the prediction of LAE when combined with conventional markers.
Post-ROsc ecG pREdictS Survival after out-of hospital cardiac arrest: validation of the PROGRESS score
Authors: Lopiano C , Pontremoli S , Bendotti S , Primi R , Currao A , Baldi E , Fasolino A , Citterio B , Vicini Scajola L , Quilico F , Giannino E , Paggi M , Klersy C , Savastano S
Published: October 2024

Background

Prognostication is crucial for patients with an out-of-hospital cardiac arrest (OHCA) both during resuscitation and after return of spontaneous circulation (ROSC) and early prognostication is still a challenge. At this regard, we proposed the PROGRESS score: a post-ROSC 12-lead ECG features’-based score to predict 30-day survival.

Purpose

The aim of the present study is to validate the PROGRESS score on a larger population of post-OHCA patients and to test its performance even after correction for patients’ and events’ characteristics, contained in the UB-ROSC score, could increase its discrimination ability.

Methods

Cardiac arrest cases were retrieved from the Lombardy Cardiac Arrest Registry (LombardiaCARe) from January 2015 to December 2022. We considered only patients with a post-ROSC 12-lead ECG and all the variables for UB-ROSC calculation available. The PROGRESS score considers age, sex, number of segments with ST elevation, QRS width, and Brugada pattern and from 0 to 26 identifies three categories of risk of death at 30 days (low: 0-4; intermediate: 5-7; high: 8-26). The UB-ROSC score considers age, aetiology, location, witnessed OHCA, bystander cardiopulmonary resuscitation (CPR), emergency medical service (EMS) arrival time and type of presenting rhythm. The performance of the PROGRESS score, in terms of discriminatory power of calibration, was tested both alone and after correction for UB-ROSC score.

Results

We considered 940 OHCAs of whom 63.9% were males with a median age of 70 [59.5-79]. 30-day survival was 37.9%, 63.1% and 64.5% in high, intermediate, and low risk groups respectively.

PROGRESS score was shown to discriminate high-risk patients from low-risk ones [HR 1.97 (95% CI 1.42-2.73), p-value <0.001], (Harrel-C= 0.58). After correction for UB-ROSC score both calibration and discrimination improved (Harrel-C = 0.70).

Conclusions

The PROGRESS score was confirmed to predict the risk of death at 30 days in patients resuscitated from an OHCA and its discriminatory power was increased by correction for the UB-ROSC score. The use of this two scores in the field allows risk stratification during resuscitation manoeuvres and in post-ROSC care, which is essential to guide resource allocation.
Mineralocorticoid receptor antagonist therapy in patients with ischemic heart failure and ventricular tachycardia: a comparative analysis of spironolactone vs. eplerenone
Authors: Szakal I , Komlosi F , Toth P , Vamosi P , Arnoth B , Bohus G Y , Szegedi N , Sallo Z , Perge P , Osztheimer I , Merkely B , Geller L , Nagy K V
Published: October 2024

Background

Mineralocorticoid receptor antagonists (MRAs) are a cornerstone of heart failure therapy and have been shown to reduce the incidence of sudden cardiac death. However, a direct comparison between spironolactone and eplerenone in patients who present ventricular tachycardia (VT) is lacking.

Purpose

This study aimed to compare the effect of spironolactone and eplerenone on VT recurrence in patients with ischemic heart disease (IHD) hospitalized for VT episodes.

Methods

Our data utilized a registry of 405 patients with IHD and HF, who were hospitalized for an episode of sustained VT and received MRA therapy. We performed propensity score matching based on age, hypertension, diabetes, history of acute myocardial infarction, left ventricular ejection fraction (LVEF) and presentation with incessant VT. The matched population included 200 patients, stratified into two equivalent groups. Cox regression analysis was performed to identify predictors of VT recurrence, with Kaplan-Meier curves facilitating time-to-event analyses.

Results

The median age was 69 years and the majority (91%) were male. One-third had an ICD, and 41 patients (20%) had CRT. The median LVEF was 30%, 23 patients (12%) presented with an electrical storm, while 18 (9%) had incessant VT. VT led to hemodynamic instability in 91 cases (46%). Ablation was performed in 47 patients (24%), while 1 required mechanical circulatory support. Ablation was performed in 47 patients (24%), while 1 required mechanical circulatory support. Patients were followed for at least a year and median follow-up time was 414 days. A total of 78 patients had VT recurrence and 117 patients died. Eplerenone use significantly reduced the risk of VT recurrence compared to spironolactone (HR: 0.59 [0.37-0.93], p=0.023). This effect was consistent in the multivariate model as well (p=0.007).

Conclusions

Eplerenone use may confer a greater protective effect against VT recurrence in patients with IHD and sustained VT. Further studies are required to confirm these preliminary findings.
Larger QRS but better hemodynamic function after high output His bundle pacing in patients with heart failure and narrow QRS. A paradox or a new concept?
Authors: Katsouras G , Stavrakis S , Perniciaro V , Semeraro A , Duni N , Dadamo M , Fortunato F , Sgarra L , Grimaldi M
Published: October 2024

Background

QRS duration is an important factor in determining Cardiac Resynchronisation Therapy (CRT) response and a useful surrogate for electromechanical dyssynchrony. However, we don’t have studies confirming this concept in conduction system pacing.

Purpose

We performed His Bundle Pacing (HBP) with high output (3.5V/1msec) in HF patients with dilated or ischemic cardiomyopathy and narrow QRS to evaluate hemodynamic benefit independent of the QRS duration or AV delay shortening.

Methods

14 patients with dilated (7 patients) or ischemic (7 patients) cardiomyopathy (EF<35%) and narrow QRS (<120ms) were referred for implantation of a defibrillator. We implanted an ICD- HBP system, and we collected clinical, echocardiographic, and electrocardiographic data.

Results

We obtained HBP in all 14 patients successfully. PQ after implantation was shorter from 172±48 to 143±16 (P=0.048) so as to pace the ventricle. Baseline QRS duration increased after pacing from 110±15 to 123±16ms (P=0.008) as measured by ECG analyzer. Despite this increase in QRS duration basal mean EF increased from 30±4% to 46±10% (P<0.001) after a median follow-up of 17 months. Left ventricular end-diastolic diameter and left ventricular end-diastolic volume decreased from 62±5 to 57±5mm (P=0.013) and from 195±69 to 126±27ml (P<0.001), respectively. Left ventricular end-systolic volume decreased from 139±58 to 69±27 (P<0.001). TAPSE increased from 19±4 to 27±4. NYHA class decreased by one class in every patient after only one month. HBP threshold was 1.05V±0.7/1msec and raised to 1.33±0.93/1msec (due mainly to 2 patients with very high threshold). The impedance was 588±109 and decreased to 484±69 Ohms. R-wave at implant was 3.2±1.8mV. In 2 out of 14 patients, threshold increased but was still less than 3.5V/1msec.

Conclusions

HBP in HF patients with dilated or ischemic cardiomyopathy and narrow QRS improves hemodynamic function in right and left ventricle and decreases NYHA class. This benefit appears to be produced by a higher stimulation output despite a larger QRS after pacing. We exclude that a very short AV delay could be favorable, by measuring acute EF changes only after increasing the pacing output without AV delay modifications. To our knowledge these are the first cases of beneficial HBP in HF patients with narrow QRS. Interestingly, larger QRS corresponds to higher EF in patients with high output HIs Bundle Pacing.
Remote monitoring of implantable cardioverter defibrillators: a systematic review and meta-analysis of randomised controlled trials
Authors: Stefil M , O'shea C J , Middeldorp M , Hendriks J M , Lau D H , Emami M , Thiyagarajah A , Ariyaratnam J , Fitzgerald J , Young G , Roberts-Thomson K , Sanders P
Published: October 2024

Background

Remote monitoring (RM) of implantable cardioverter defibrillators (ICD) has been widely adopted as the standard follow-up strategy [1]. Observational data [2,3] has suggested morbidity and mortality reduction associated with RM compared to traditional in-person ICD follow-up, however, randomised controlled trials (RCTs) demonstrate heterogeneous results.

Purpose

To assess the impact of RM of ICDs on morbidity and mortality through a systematic review and meta-analysis of RCTs comparing RM versus in-person follow-up.

Methods

PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and reference lists were searched for RCTs evaluating RM compared to in-person follow-up of patients with ICDs or cardiac resynchronisation therapy with defibrillator (CRT-D) devices. Meta-analyses of all-cause mortality, cardiovascular (CVD) hospitalisation and inappropriate ICD shock rates were performed.

Results

Literature search identified 1011 relevant publications, out of which 15 RCTs [4-18] involving a total of 7579 patients (13 RCTs reporting mortality rate, 7 RCTs reporting CVD hospitalisation rate, 6 RCTs reporting inappropriate ICD shock rate) met the inclusion criteria. Pooled analyses demonstrated that RM is not associated with a significant reduction in all-cause mortality (OR 0.95; 95% CI 0.78-1.16; p=0.60)(Figure 1, panel a) or odds of CVD hospitalisation (OR 0.95; 95% CI 0.72-1.25; p=0.70) (Figure 1, panel b). RM was, however, shown to be associated with significantly lower odds of receiving an inappropriate ICD shock compared to the control group (OR 0.63; 95% CI 0.46-0.88; p=0.006) (Figure 1, panel c). The IN-TIME study (the only RCT that independently reached statistical significance in terms of RM effect on mortality) enrolled patients exclusively with a Biotronik ICD or CRT-D; this raised the question as to whether the choice of vendor had an impact on mortality. Our subgroup analysis of the Biotronik device studies demonstrated that there was no significant all-cause mortality benefit (OR 0.87, 95% CI 0.59-1.27; p=0.46).

Conclusions

This meta-analysis of 15 RCTs including 7579 patients suggests that RM of ICDs is associated with a reduction in inappropriate ICD shocks, without a significant reduction in mortality or CVD hospitalisation when compared to in-person follow-up. Further studies comparing different RM processing and alert response models are warranted.
Infection management in the extravascular implantable cardioverter defibrillator: experience from the EV ICD Pivotal study
Authors: Clementy N , Crozier I , Murgatroyd F , Boersma L V A , Manlucu J , Knight B P , Leclercq C , Birgersdotter-Green U M , Mattioni T , Sholevar D , Hersi A , Wiggenhorn C , Friedman P
Published: October 2024

Background

The extravascular implantable cardioverter defibrillator (EV ICD) has recently emerged as an option for guideline indicated ICD patients. Results from the EV ICD Pilot and Pivotal studies demonstrated that the device can provide safe and effective therapy through chronic follow up. Lead placement outside the vasculature has the potential to reduce systemic infections. Infection occurrence and management details from the Pivotal are reported.

Purpose

To report on details of infection occurrence and management from the EV ICD Pivotal study.

Methods

The EV ICD Pivotal study was an international, prospective, 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.

Results

In the EV ICD Pivotal study, 316 patients had an implant attempt, (74.7% male, age 53.8±13.1 years, 82% primary prevention, LVEF of 38.9%±15.4%, and NYHA Class I [23.7%] or II/III [65.5%]), of which 15 had a system or procedure-related infection (4.7%, 9 - 737 days post-implant) through an average 16.2 months follow-up. Of these infections, 8 were classified as major complications, 3 as minor, and 4 as observations. Most (n=9) infections were addressed through medication with or without wound care (2.8% of patients) while 6 (1.9% of patients) resulted in system removal. There was a single lead-related infection addressed through system explant. However, there were no reports of mediastinitis, sepsis, or endocarditis. No system removal resulted in sequelae.

Conclusions

Infection rates observed in the EV ICD Pivotal study were similar to those reported in the subcutaneous implantable cardioverter defibrillator. The results from this study support that EV ICD related infections are treatable with antibiotic therapy or system removal. No system or procedure-related systemic infections such as mediastinitis, sepsis, or endocarditis have been reported in the Pivotal study.
Associations of different definitions of iron deficiency with cardiac structure and function, congestion, exercise capacity and prognosis in heart failure
Authors: Pugliese N , De Biase N , Del Punta L , L'hoyes W , Pellicori P , Cleland J G F , Masini G , Masi S , Verwerft J
Published: October 2024

Background

It is uncertain how best to diagnose iron deficiency (ID) in patients with heart failure (HF) as different ID definitions have been proposed with discordant results.

Objectives

To assess the relationship of different ID definitions with cardiac structure and function, congestion, exercise capacity, and prognosis in outpatients with HF.

Methods

ID was defined according to guidelines (G-ID: ferritin <100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation [TSAT] <20%) or as TSAT <20%. Alternative definitions (iron <13 ¼mol/L, ferritin <100 and <300 ng/mL) were explored. Relationship with rest and exercise ultrasound findings, cardiopulmonary exercise testing and a composite endpoint of cardiovascular hospitalisations or all-cause mortality were assessed.

Results

Of 1502 patients (72% with left ventricular ejection fraction [LVEF] ≥50%), 471 (31%) had TSAT <20%, while 728 (48%) had G-ID. Compared to those without ID, patients with TSAT <20% or G-ID showed impaired cardiac structure and function at rest and peak exercise and lower peak oxygen consumption; they were also more likely to display a discontinuous renal venous flow pattern and more lung B-lines. Only TSAT <20% was associated with significant inferior vena cava dilatation. Lower TSAT, iron and haemoglobin were associated with more severe effort intolerance and ultrasound signs of congestion, while ferritin and LVEF were not (Picture 1). During a median follow-up of 16 months, 62 (4%) patients died, and 244 (16%) were hospitalised for cardiovascular reasons. No patients were hospitalised immediately after the enrolment visit because of clinical findings. At Kaplan-Meier analyses, TSAT <20% was associated with a greater risk of adverse events, as were iron ≤13 ¼mol/L, ferritin ≥300 ng/mL and <100 ng/mL (p <0.01 vs ferritin 100-299 ng/mL) and G-ID (Picture 2). After adjusting for age, sex, diabetes, haemoglobin, estimated glomerular filtration rate (eGFR), NT-proBNP, rest LVEF and peak VO2 <16 mL/kg/min, TSAT <20% and iron ≤13 ¼mol/L were associated with worse outcomes (hazard ratio 2.41, 95% confidence interval 1.85-3.14 and 1.90, 1.46-2.47), while G-ID or ferritin <100 or <300 ng/mL were not (Picture 1).

Conclusions

In outpatients with HF, TSAT <20% is more consistently associated with echocardiographic signs of poorer functional capacity and multi-organ congestion than other ID definitions. TSAT <20% and iron ≤13 ¼mol/L, but not G-ID or ferritin-based ID, seem to predict a worse prognosis.Picture 1Picture 2
Epicardial carbohydrate antigen 125 (CA-125) levels, associated with neutrophils activity in heart failure: No differences regarding sex
Authors: Eiras S , Fu X , De La Espriella R , Basdas R , Sanchez-Lopez D , Iglesias-Alvarez D , Nunez-Camano J R , Garcia-Vega D , Martinez-Cereijo J M , Fernandez A L , Reija L , Sahel S , Nunez J , Gonzalez-Juanatey J R
Published: October 2024

Background

Carbohydrate antigen 125 (CA125), is the name of the soluble part of mucin-16, after being cleaved, which is detected and increased into circulation in congestive heart failure (HF) patients.

Purpose

We aimed to study plasma and epicardial fat markers related to inflammation, fibrosis, adiposity, and its association with plasma and epicardial CA125 for understanding the underlying mechanisms of heart failure and the differences between men and women.

Methods

We have included women and men undergoing open heart surgery (n=134). Epicardial fat biopsy and blood were obtained before the procedure under signed consent. Immunohistochemistry, ELISA, multiplex-Luminex, and real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers.

Results

Out of 135, 57 patients suffered heart failure (HF). CA125 was expressed on the epicardium. Their levels were positively related to neutrophils, monocytes, and fibroblasts-related markers and negatively to adiposity markers. Both, plasma and epicardial CA125 levels were increased in HF patients. In this group of patients, epicardial CA125 levels were positively associated with circulating and local neutrophil activity, measured by defensin 3 levels. After testing all markers between women and men in HF patients, we observed similar levels in plasma and epicardial CA125. However, higher plasma and epicardial adiposity markers and lower mesothelial marker ITLN-1 were detected in women than in men.

Conclusion

CA125 is expressed in epicardial cells and its higher levels in HF might explain the higher detected levels in plasma. Its association with local and peripheral neutrophils-related markers with CA125 suggests its common pathophysiological mechanism in women and men. However, high plasma and epicardial adiposity and low mesothelial marker ITNL-1 in epicardium in women might explain the differential mechanism in HF.
Identification and validation of circulating microRNAs as biomarkers for heart failure with preserved ejection fraction
Authors: Zhang L , Yang Y
Published: October 2024

Background

Heart failure (HF) is a syndrome due to cardiac insufficiency, manifested by excessive volume overload, increased sympathetic activity, and circulatory redistribution [1]. Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 40%-50% of the total HF events, and its development is often accompanied by various complications, including hypertension, obesity, and metabolic syndrome. Biomarker associations in heart failure with reduced ejection fraction were mostly cardiac stretch based, while many biomarkers of HFpEF are also associated with inflammation [2]. To date, treatments that effectively improve the clinical prognosis of HFpEF are relatively limited, thus HFpEF remains one of the challenges that needs to be further explored. A full understanding of the molecular mechanisms of HFpEF is essential to improve the early diagnosis, treatment and prognosis of these patients.

Purpose

The study aims to explore key circulating miRNAs and related molecular pathways in HFpEF patients through bioinformatics analysis and machine learning, and to further validate them using a double-hit HFpEF mouse model.

Methods

We downloaded HF datasets including circulating miRNA expression profiles from the GEO database. LASSO regression, SVM-RFE, Random Forest and XGboost algorithm were conducted to identify key miRNAs for diagnostic model construction. We used R software, GO, KEGG and Cytoscape to better understand the functions of key miRNA targets. Besides, the mRNA-miRNA interaction networks were predicted by starbase. We also constructed a HFpEF mouse model subjected to high fat diet and L-NAME (0.5 g/L) in drinking water to discover the correlation between the screened circulating miRNA and HFpEF.

Results

After differential expression analysis of the combined HFpEF dataset, we identified 37 differentially circulating miRNAs, of which 15 were down-regulated and 22 were up-regulated. Subsequently, we screened by machine learning and identified 4 key miRNAs that may be involved in the progression of HFpEF, including hsa-miR-645, hsa-miR-296-5p, hsa-miR-199b-5p, and hsa-miR-509-3-5p. We validated these miRNAs based on their expression, and the ROC plots suggest that these miRNAs may have diagnostic capability in HFpEF. The results of GO and KEGG enrichment analyses showed that the target genes of the differentiated miRNAs were mainly enriched in the MAPK signaling pathway, mTOR signaling pathway, protein processing in endoplasmic reticulum, hippo signaling pathway, cell cycle, Foxo signaling pathway, hypertrophic cardiomyopathy, dilated cardiomyopathy, and circadian rhythm. The mRNA-miRNA interaction networks suggested that TMEM135 was regulated by both has-miR-199b-5p and hsa-miR-296-5p. The RT-PCR results also suggested that miR-199b-5p was upregulated in the HFpEF mice.

Conclusion

We validated 4 circulating miRNAs with strong correlation to HFpEF, which provide a more reliable basis for pre-symptomatic diagnosis.