bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact on preoperative estimation of atrial mechanical amplitudes with vdd leadless pacemaker
Authors: Komai Y , Kajiyama T K , Takanashi Y T , Yoshino Y Y , Ryuzaki S R , Chiba T C , Ito R I , Nakano M N , Kondo Y K , Kobayashi Y K
Published: October 2024

Background

It would be useful to determine whether the device can sense the mechanical atrial amplitude (A4) before the implantation of a VDD leadless pacemaker (Micra AV^RT, Medtronic, US).

Purpose

To evaluate whether identifiable A4 is associated with preoperative echocardiographic parameters.

Methods

Echocardiographic measurements were performed to quantify atrial motion of the interventricular septum in patients who received a leadless pacemaker implantation. We visually divided the septum into five segments from the base to the apex. As shown in Figure 1, the myocardial velocity of each segment measured on tissue doppler imaging (TDI) was defined as EV1, EV2, EV3, EV4, and EV5 (m/s), respectively. After the implantation, amplitude of A4 was compared to the local EV.

Results

We retrospectively analyzed 30 patients who had Micra AV implanted into the right ventricular septum by imaging examination and had measurable EV for each segment. The mean age was 82.3±7.8 years, 15 (50%) patients were female, 11 (37%) patients had organic heart disease, and 23 (77%) patients had atrial ventricular block. The mean LVEF and A4 amplitude were 60.4 ± 8.9% and 2.7 ± 1.8 m/s^2, respectively, and the mean atrial mechanical sensing rate (AMSR) was 79.9±24.0%. The A4 amplitude was positively correlated to the AMSR (r=0.48), while the AMSR was significantly better in patients with A4 amplitude over 1.0 m/s^2 (88.0 ± 10.4% vs. 41.0 ± 33.6%, p=0.04). The A4 amplitude was correlated to the EV of the implantation site estimated from fluoroscopy and echocardiography (r=0.62) in Figure 2. 24 patients had local EV over 3.0 cm/s, and among them, 22 (92%) patients had A4 amplitude over 1.0 m/s^2.

Conclusion

Local EV over 3.0 cm/s, as determined by preoperative echocardiography, might predict high-frequency AMSR.
Atrial rates during treated ventricular tachycardia in patients with implantable cardioverter defibrillators: clinical implications of a vagal sinus node response
Authors: Martin R , Maclean E , Sevier L , Page H , Ganeswaran T , Lamelas R , Whittaker-Axon S , Martin S , Ahluwalia N , Tonko J , Monkhouse C , Lambiase P , Dhinoja M
Published: October 2024

Introduction

Autonomic tone plays an important role in the genesis and sustenance of ventricular tachycardia (VT). Whilst sympathetic hyperactivity is an established driver of ventricular arrhythmias, sinus node response during VT varies broadly between patients, and can be paradoxical.

Purpose

We hypothesized that device-detected changes in sinus node rate could be an important surrogate of the autonomic response to VT, and may exert significant – and potentially modifiable – haemodynamic consequences independent of ventricular activity.

Methods

Device electrograms were analysed from consecutive patients with dual chamber implantable cardioverter defibrillators (ICDs) requiring anti-tachycardia pacing (ATP) or defibrillation for sustained monomorphic VT. Atrial rates were measured before VT onset (‘baseline’) and again at the point of detection by the device. Sinus node response was characterized as ‘stable’ (atrial rate remained within 10% of baseline), ‘sympathetic’ (atrial rate increased >10%) or ‘vagal’ (atrial rate decreased >10%). Patients who did not maintain ventriculoatrial dissociation or who presented in atrial tachyarrhythmia were excluded. Symptoms and electrical response to ICD therapies were recorded.

Results

172 treated episodes of VT were included from 97 patients (median age: 69 years, 65% male, 31% ischaemic cardiomyopathy, median ventricular rate: 205bpm, median ejection fraction: 30%). Sinus node response was stable in 55%, sympathetic in 24% and vagal in 21%. A vagal response was associated with ATP-refractory VT (OR: 2.2 (1.1-4.8) p=0.03) and, when adjusting for ventricular rate, was independently associated with symptoms of presyncope or syncope (adjusted OR: 6 (2.7-13.7), p<0.0001).

Conclusions

This preliminary analysis suggests that a vagal sinus node response during VT is associated with adverse outcomes in ICD patients. Vagolytic therapy has recently been demonstrated to improve haemodynamic tolerance during VT ablation; whether supportive atrial pacing during VT could mitigate symptoms and potentiate arrhythmia termination in ICD patients warrants further exploration.

Figure 1: Change in sinus node rate during sustained monomorphic ventricular tachycardia in patients with dual chamber ICDs, stratified by the occurrence of presyncopal symptoms or syncopeFigure 1
All-cause mortality and incidence of appropriate therapy from a primary preventive implantable cardioverter defibrillator in patients with non-ischemic dilated cardiomyopathy
Authors: Nguyen T M , Melichova D , Salte I M , Gjertsen E , Heggelund G , Kleiven Ø , Brunvand H , Edvardsen T , Haugaa K
Published: October 2024

Background

The DANISH study published in 2016 indicated limited benefit of primary prevention implantable cardioverter-defibrillator (ICD) in patients with non-ischemic dilated cardiomyopathy (niDCM). We aimed to investigate the long-term outcome and incidence of ICD therapy in patients with niDCM implanted on primary prevention indication during 2014-2022.

Methods

A total of 116 patients with niDCM were prospectively included for primary prevention ICD implantation between 2014 and 2022 in the multicenter IMPROVE study (clinical trials NCT02286908). All patients were examined with electrocardiogram, echocardiography and blood sampling at inclusion. The primary outcome was all-cause mortality, and the secondary outcome was appropriate ICD therapy. Outcomes were compared in patients included from 2014 to end of 2016 (DCM2014-16, n=49) and from 2017-2022 (DCM2017-22, n=67).

Results

At inclusion, patients in DCM2017-22 were younger (54 years [interquartile range (IQR) 44-68] vs. 64 years [IQR 55-70], p=0.001), had higher left ventricular ejection fraction (LVEF) (33% [IQR 25-38] vs. 24% [IQR 21-31], p<0.001) and less frequently received cardiac-resynchronization therapy defibrillator (6% vs. 29%, p=0.001) compared to DCM2014-16. Over a median 4.4-year follow-up, the all-cause mortality was 14%, of which 10% occurred in the DCM2017-22 patients (2.6 events/100 person-years), and 18% in the DCM2014-16 patients (4.0 events/100 person-years), p=0.38. There was no difference in appropriate ICD therapy between the two groups (p=0.90).

Conclusion

Patients receiving primary prevention ICD for niDCM after publication of the DANISH study were younger with higher LVEF, indicating a change in clinical practice after the publication. Despite this, there was no significant reduction in all-cause mortality or difference in appropriate ICD therapies. Unchanged mortality and event-rates may indicate the correct identification of high-risk patients.
Assessment of quality of life and ICD shock-related anxiety in Asian patients with implantable cardioverter defibrillator in the PainFree SST study
Authors: Kondo Y , Sears S F , Bart G , Sterns L D , Schloss E J , Meijer A , Auricchio A , Kurita T
Published: October 2024

Background

The implantable cardioverter defibrillator (ICD) reduces mortality in patients at risk of sudden cardiac death. However, it is not known if the psychological status of ICD patients differs by geography. The aim of this analysis is to compare Quality of Life (QoL) and ICD shock-related anxiety between ICD patients in Asian with those in other countries.

Methods

The PainFree SST study was a prospective, multicenter, global study that enrolled 2770 patients including 225 from from Asia (181 from Japan, 25 from India, and 19 from Malaysia). The EuroQol 5-D (EQ-5D) measured QoL and the Florida Shock Anxiety Scale (FSAS) measured ICD shock-related anxiety. These questionnaires were administered bi-annually and monthly for 6 months after a shock. Change in QoL and shock anxiety was analyzed used linear mixed models for repeated measures.

Results: Both the EQ-5D health score and FSAS score were higher in Asian patients compared to patients in the other countries post-implant (EQ-5D: 69.5 ± 18.3 points vs 66.5 ± 19.3 points, p<0.0001, FSAS: 19.7 ± 9.4 points vs 16.4 ± 7.7 points, p<0.0001), and stayed higher for the entire follow-up period (Figure 1). The EQ-5D health score was significantly reduced after a shock (Asian: -18.1 points, p<0.0001; other countries: -7.5 points, p<0.0001) with a greater reduction in Asian patients (p=0.0035) . Recovery in the month following a shock was greater in Asian patients (+19.8 vs +3.6 points, p<0.0001). The FSAS score was significantly increased after a shock (Asian: +6.4 points, p<0.0001; other countries: +4.8 points, p<0.0001) and the increase was similar between geographies (p=0.20). The recovery effect at 1 month was greater in Asian patients (-5.8 vs -1.7 points, p=0.0003) (Figure 2).

Conclusions

Asian patients were more anxious about a shock in spite of greater QoL, compared with those in other countries. After a shock, Asian patients had a greater decrease in QoL and a similar increase in anxiety but recovery was greater in both measures in the month following a shock.Figure 1Figure 2
Dual-chamber CRT-D using ICD lead implantation in the LBBAP position
Authors: Imnadze G , Bocchini Y , Fink T , Eitz T , Sciacca V , Niehaus C , El Hamriti M , Khalaph M , Guckel D , Braun M , Didenko M , Sohns C , Sommer P
Published: October 2024

Background

Interest in conduction system pacing (CSP) has increased in recent years. For left bundle branch area pacing (LBBAP), 4F and 6F pacing leads have been shown to be effective and safe. No information is available on the potential use of ICD leads for LBBAP.

Aim

The objective of the study was to demonstrate the feasibility of implanting an ICD lead in the LBBAP position to reduce the number of leads for CRT-D therapy.

Patients and Methods

We implanted the 7F ICD lead in the LBBAP position through a new 10F CSP delivery sheath in ten consecutive patients. Periprocedural data, QRS morphology and degree of QRS reduction were analyzed.

Results

Ten consecutive patients (one female) aged 69.5±9.2 years were treated with the above-mentioned method. Eight patients had ischemic cardiomyopathy and two patients had nonischemic cardiomyopathy. All patients had a CRT-D indication. Eight patients had a wide QRS complex with complete LBB and a QRS complex of 184.8±25.8 ms. Two patients had a narrow QRS complex but first-degree AV block with a PR interval greater than 240 ms. Left ventricular ejection fraction was 31.8±8.6%. Operative and fluoroscopy times were 103.6±30.3 minutes and 10.5±6.1 minutes, respectively. On average, 1.7 ± 0.6 screwing attempts were required per patient. The intraprocedural LBBAP threshold was 0.78±0.6V/1.0ms, the impedance was 530.8±86.5 ohm, and the R-wave amplitude was 9±3.3mV. The unipolar paced QRS complex was 123.6±15.9ms, the bipolar paced QRS complex was 129.5±12.8ms, and the bipolar paced QRS complex on the next day was 133.3±11.7.

The mean duration from stimulus to R-wave peak in lead V6 was 82.9 ± 19.7 ms. The R-wave interpeak interval between leads V6 and V1 was 43.4 ± 9.7 ms. All but one patient received an effective defibrillation threshold test at 30J (n=8) and 36J (n=1). One patient was not tested during the procedure due to high risk.

Conclusion

This first-in-human study of ICD lead implantation in the LBBAP position demonstrated its feasibility and efficacy in achieving conduction system stimulation. This approach may lead to a reduction in the number of leads implanted for cardiac resynchronization therapy.

Figure 1. A- RAO view, angiography of the RV for verification of the TVA-summit. B- LAO view, angiography from the CSP- sheath after reaching final position of the LBBAP lead (right sided interventricular septum - yellow dotted line). C – 12 lead ECG (speed 50mm/sec) demonstrating paced and native QRS complexes. D – Fluoroscopy in RAO view, final result. E – Fluoroscopy in LAO view, final result. F – Transthoracic echocardiography the next day (4Ch view) demonstrates optimal LBBAP lead position.. RAO – right anterior oblique; LAO – left anterior oblique; TVA – tricuspid valve anulus; CSP – conduction system pacing; LBBAP – left bundle branch area pacing.Figure 1.
LBBAP versus conventional CRT reimplantation after transvenous lead extraction: report from a monocentric experience
Authors: Baroni M , Preda A , Carbonaro M , Fortuna M , Caccia A , Guarracini F , Colombo G , Vargiu S , Varrenti M , Frontera A , Gigli L , Mazzone P
Published: October 2024

Background

Cardiac resynchronization therapy – defibrillator (CRT-D) reimplantation after transvenous lead extraction (TLE) can be challenging due to fibrotic remnants and absence of target veins. Left bundle branch area pacing (LBBAP) is emerging as an alternative to conventional CRT, but data is lacking about its feasibility after TLE.

Purpose

To explore the feasibility and safety of LBBAP as alternative to conventional CRT though epicardial pacing (EP) in patients undergoing CRT-D TLE.

Methods

We prospectively enrolled all patients admitted for complete CRT-D extraction and replacement from July 2022 to September 2023. At the moment of reimplantation, the choice between EP and LBBAP was made on the basis of posterolateral CS branches viability at post-extraction CS venography. Procedural success was defined as effective stimulation and absence of major complications while the primary endpoints were procedural time, QRS complex duration and electrical lead parameters. Patients undergoing LBBAP and EP reimplantation were compared.

Results

Twenty-six patients were enrolled (mean age 68.3 ± 7.2 years, p = 0.538; 12% females, p = 0.859). The most frequent cause of device extraction was pocket infection (58%, p = 0.773). Seventeen (65%, p = 0.783) patients had estimated high risk of procedural severe complications measured by EROS score. Overall, 80 leads were extracted. Mechanical extractors and snares were deemed necessary in 35 cases (43%, p = 0.917) and in 2 cases, respectively. Almost all patients (n=25, 96%) underwent right-sided reimplantation. Procedural success was achieved in 24 cases (92%). Compared to standard CRT through EP, LBBAP reimplantation accounted for a faster procedure (109.5 ± 34.2 vs. 126.5 ± 46.8 min; p = <0.001), less radiologic exposure (877.0 ± 234.6 vs. 1332.0 ± 515.1 sec, p <0.001) and better ventricular pacing thresholds (0.7± 0.1 vs. 1.8± 0.6 V, p <0.001). Despite a similar pre-extraction paced QRS duration (127.4 ± 13.8 vs. 133.0 ± 14.4 msec; p = 0.610), LBBAP reported significant improvement in final QRS duration (105.0 ± 13.1 vs. 127.1 ± 10.4 msec, p < 0.001) with major reduction in QRS duration (- 10.9 ± 7.5 vs - 6.8 ± 10.1, p < 0.001).

Conclusion

After a CRT TLE procedure, LBBAP reimplantation accounted for lower procedure duration, lower radiologic exposure, narrower QRS and lower ventricular pacing thresholds, demonstrating to be a valuable alternative to EP.
A larger reduction of spatial mean QRS-T angle during cardiac resynchronisation therapy is associated with a lower risk of mortality and heart failure hospitalisation
Authors: Marinko S , Cortez D , Platonov P G , Bergfeldt L , Borgquist R
Published: October 2024

Background

Predicting clinical outcome in heart failure patients undergoing cardiac resynchronization therapy (CRT) remains challenging, necessitating improved risk stratification for CRT recipients. Previous studies have shown an association between large spatial peak and mean QRS-T angles and cardiovascular disease. Little is known, however, about their relation to clinical outcome following CRT.

Purpose

To investigate the association between spatial peak and mean QRS-T angles and long-term clinical outcome following CRT initiation.

Methods

All patients with native LBBB receiving CRT at a large-volume tertiary care center between 2015 and 2020 were retrospectively evaluated. Spatial peak and mean QRS-T angles were derived from digital pre- and post-CRT 12-lead ECGs that were processed using Glasgow algorithm and Kors’ regression transformation. The QRS-T angles and their change after CRT were analyzed in relation to the primary composite endpoint of heart failure hospitalisation or all-cause mortality using Cox regression analysis adjusted for clinical covariates (age, gender, CRT-P or CRT-D, secondary ICD indication, ischemic etiology, NYHA class, LVEF, diabetes, atrial fibrillation, baseline QRS duration, NT-proBNP, and eGFR).

Results

The study group comprised 250 patients (a median age [Q1–Q3] of 72.2 years [64.5–76.3]; 22% female; 58% New York Heart Association (NYHA) class III-IV; LVEF 27% [22–30]) who were followed over a median follow-up time of 4.5 years [3.2–5.8] after CRT implantation. The median post-CRT spatial peak and mean QRS-angles were 142° [116–160] and 152° [127–166], and the median angle was decreased by 16° [-0.6–41] and 14° [-0.4–38], respectively. Both a larger post-CRT mean QRS-T angle (HR 1.20, 95%CI 1.08-1.33, p=<.001) and peak QRS-T angle (HR 1.08, 95%CI 1.01-1.17, p=0.046) were associated with the primary endpoint. A larger reduction of mean QRS-T angle, but not peak QRS-T angle, was associated with a risk reduction (HR 0.87, 95%CI 0.79-0.95, p<0.003). In Kaplan-Meier analysis, patients with a post-CRT mean QRS-T angle above median had a higher risk of reaching the endpoint (log-rank p=0.002, Figure 1).

Conclusion

Our results show that a larger magnitude of the post-CRT spatial peak and mean QRS-T angles, and a larger reduction of the latter, are associated with long-term heart failure hospitalisation and death. These findings suggest that spatial QRS-T angle may have a potential role in refined risk stratification of CRT patients.Figure 1.K-M curve spatial mean QRS-T
The effect of the age at the time of targeting a lead implantation on the difficulty with the transvenous lead extraction technique
Authors: Yamada T
Published: October 2024

Background

In transvenous lead removal procedures, the number of years since the lead implantation is an indicator of procedural difficulty and complications. However, even with the same number of years since the lead implantation, we considered the possibility that a younger age at the time of the implantation (AoI) would increase the difficulty of the procedure.

Objective

To elucidate the procedural difficulty in the transvenous lead extraction procedure according to the age at the time of targeting the lead implantation.

Method

A total of 471 consecutive transvenous lead extraction cases were analyzed. The patient AoI of the oldest lead in extraction procedure cases was divided into two groups: those younger than 60 years (implant age <60 yrs old: AoI<60) and those older than 60 years (implant age ≧60 yrs old: AoI≧60). The analysis was conducted by the number of years since the lead implantation (<10 years: group A, 10 to 20 years: group B, and >20 years: group C).

Results

The number of AoI<60 and AoI≧60 patients were 60 and 254 (Group A), 51 and 56 (Group B), and 41 and 9 (Group C). The patient age significantly differed among the groups between an AoI<60 and AoI≧60 (group A: 51.7 vs. 77.1; P<0.001, group B: 61.6 vs. 83.1; P<0.001, group C: 71.2 vs. 88; P<0.001). But the oldest dwell time (years) was similar for all groups (group A: 4.6 vs. 4.2; P=0.324, group B: 14.2 vs. 13.5; P=0.148, and group C: 25.7 vs. 22.6; P=0.097). The complete removal rate (group A: 97.7% vs. 98.4%; P=0.722, group B: 90.4% vs. 93.3%; P=0.567, and group C: 78.05 vs. 90.95; P=0.337) and major complication-free rate (group A: 98.8% vs. 100%; P=0.391, group B: 96.2% vs. 100%; P=0.125, and group C: 90.2% vs. 100%; P=0.281) were not statistically significant in all groups but were higher for an AoI≧60. An AoI<60 resulted in a longer procedure time (group A: 78.4 min. vs. 65.3 min.; P=0.006, group B: 96.0 min. vs. 72.3 min.; P=0.002, and group C: 100.9 min. vs. 94.8 min.; P=0.709), longer fluoroscopy time (group A: 12.0 min. vs. 10.2 min.; P=0.247, group B: 19.2 min. vs. 11.6 min.; P=0.017, and group C: 22.2 min. vs. 16.0 min.; P=0.008), and higher number of laser pulses (group A: 779.6 vs. 433.7; P=0.002, group B: 2089.6 vs. 1032.9; P=0.017, and group C: 1509.3 vs. 831.5; P=0.201) in all groups.

Conclusion

This study suggested that the difficulty of transvenous lead extraction procedures may increase with a younger AoI, even if the lead dwelling time is the same.
Extraction of leadless and tranvenous pacemakers: occurrence, causes and complications from a national US database
Authors: Leshem-Rubinow E , Poliner I , Kazatsker M , Roguin A , Bareli M , Margolis G
Published: October 2024

Background

Leadless pacemakers are usually implanted as second line treatment in patients with increased risk for infection, difficult or obstructed vascular access, and other causes preventing an implantation of a traditional pacemaker. Data regarding the occurrence and need for leadless pacemaker extraction (LLPE) are currently absent and have not been compared to outcomes of transvenous pacemaker extraction (TLE). Moreover, leadless pacemaker implantation during TLE for active infection in being advocated without backing data. We aimed to assess the rate, causes and complications of device extraction in a large US national database.

Methods

Patients undergoing LLPE and TLE in the USA between 2016 and 2019 were identified from the National Inpatient Sample (NIS) database using ICD-10 codes. Clinical and sociodemographic data, in-hospital complications, outcomes and mortality were collected. Baseline characteristics and outcomes were compared between patients undergoing TLE and LLPE. Multivariate logistic regression identified predictors of in-hospital complications.

Results

An estimated total of 55,235 patients underwent an extraction procedure during the study period. 54,050 (97.8%) patients underwent TLE and 1,185 (2.1%) underwent LLPE. Patients who underwent LLPE were older, more likely females and had a higher comorbidity rate (Charlson-Deyo-Comorbidity-Index; 46% vs 39%, p<0.001). Etiology for LLPE was identified and reported only in 25.7% of cases, however infection causing extraction occurred in 11.4% of LLPE cases and 8% had LLPE due to device dysfunction. Main etiologies for TLE were infections (40.9%) and lead dysfunction (29.4%). In comparison to TLE, LLPE resulted in higher in-hospital mortality (7.2% vs. 3%, p<0.001) and vascular complications (2.5% vs. 1.0%, p<0.001). Multivariable analysis confirmed that LLPE was associated with more than double the risk of in-hospital mortality.

Conclusion

Extraction of leadless pacemakers due to infection is not rare. Patients undergoing LLPE have higher prevalence of vascular complications and in-hospital mortality in a US nationwide, all-comer registry.
Report of cardiac electronic device implant complications over a 7-year study period
Authors: Biniam B , Aydin A , Sadek M , Klein A , Nery P , Nair G , Davis D , Redpath C , Hansom S , Ramirez D , Green M , Birnie D , Gill D , Asif M , Golian M
Published: October 2024

Background

The global placement of cardiac implantable electronic devices (CIEDs) is on the rise. Complications linked to device implantation present a substantial burden on healthcare systems and patients alike. It is imperative to comprehend the complication rates associated with CIED procedures, enabling informed decision-making and strategic planning for patients, thereby enhancing the overall quality of care.

Purpose

We sought to determine post CIED implantation complication rates and provide operator specific complication data for quality assurance at our institution.

Methods

A comprehensive audit of all procedures completed between April 2016 to March 2023 by 14 high volume operators at a single academic center was completed. Complications and device data were extracted using electronic medical records. Complications evaluated include pneumothorax, infections, hematomas, venous thrombosis, lead perforation, and dislodgement using standardized definitions.

Results

During the 7-year period, a total of 9,467 procedures were completed. Among the cohort, 62% were male, with an average age of 74.6 ± 15.2 years. The procedural breakdown comprised 60% pacemakers, 19% ICDs, 16% CRTs and 3% ILRs. A total of 11,616 leads were implanted (3,644 RA leads and 1,110 LV leads). The overall complication rate was 3.1% (n=316): device pocket infection 0.68%, superficial infection 0.19%, lead dislodgement 0.53%, lead perforation 0.24%, pericardial effusion 0.1%, pneumothorax 0.15%, pocket hematoma 0.83%, DVT 0.36%, and hemothorax 0.02%. Complication rates per operator are shown in Figure-1.

Conclusion

Our findings indicate that the overall complication rates for CIED implants are lower than previously reported rates, and there is no significant difference between operators in overall rates of complication. This observation can be attributed to operator experience, advancements in peri-operative care and guideline-directed post-operative protocols. However, notable variations exist among operators in rates of pocket infection. The ongoing monitoring of CIED complications as a quality indicator remains a crucial benchmark, meriting annual assessments for ongoing evaluation.
Proteomic biomarkers and biological mechanisms associated with atrial fibrillation in heart failure patients
Authors: Petersen T B , Loncq De Jong M , Chin J F , Suthahar N , Akkerhuis K M , Umans V A , De Boer R A , Van Dalen B M , Brugts J J , Asselbergs F W , Boersma E , Rizopoulos D , Yap S C , Kardys I
Published: October 2024

Background

Atrial fibrillation (AF) and heart failure (HF) are intertwined conditions with high mortality rates and large impact on quality of life, and their coexistence is increasingly prevalent. Both conditions influence each other’s development and progression, and share many risk-factors—such as hypertension, obesity, diabetes mellitus and ischaemic heart disease. Moreover, their combined presence further increases the risk of hospitalization and mortality. The biological mechanisms at play in HF patients with AF may therefore differ from those in HF patients without AF.

Purpose

We aimed to describe the differences in pathophysiological pathways in HF patients with versus without AF, by identifying biomarkers associated with AF from a panel of 4210 circulating proteins and subsequently examining biological mechanisms related to these biomarkers.

Methods

We examined 377 ambulant HF patients with reduced ejection fraction from a longitudinal cohort study. We measured 4210 circulating proteins in baseline blood samples using an aptamer-based multiplex proteomic approach. Associations between AF (known AF history or AF on the baseline ECG) and the proteins were assessed using linear regression models adjusted for age, sex, kidney function and duration of HF at baseline. Associations of proteins significantly related to AF, with biological processes, were assessed using network-based clustering and subsequent enrichment analysis.

Results

The median [25th, 75th percentile] age was 64 [55, 72], 73% [274/377] were male, 28% [104/375] had NYHA-class III or IV, and 37% [139/377] had AF (either AF history: 36% [137/377] or AF on baseline ECG: 8% [30/374]). We found 71 proteins significantly associated with AF (FDR<0.05), including well-studied (e.g. troponin T, IGFBP7, MFAP4, BMP10, angiopoietin 2) and lesser studied (e.g. olfactomedin−like protein 3, keratocan, basigin) proteins in the AF domain. Our pathway analysis revealed clusters of proteins related to various underlying mechanisms, such as axon guidance, elastic fibre assembly, macrophage derived foam cell differentiation, ether lipid metabolism and amyloid-beta binding. Overviews of the significantly associated proteins and related biological mechanisms are provided in Figures 1 and 2.

Conclusion

HF patients with AF have distinct proteomic profiles and these differences are related to various biological mechanisms, many of which can be associated with atrial remodelling. This study provides an overview of the biological mechanisms behind AF in HF, confirms prior findings regarding AF-related proteins, and could guide future research in novel treatment targets and HF-AF management.Figure 1:Proteins associated with AFFigure 2:Biological mechanisms
Gene-echocardiography: unmasking the covert role of fatty acid metabolism gene mutations in adult cardiomyopathy
Authors: Zhou N
Published: October 2024

Background

Although the role of fatty acid metabolic deficiencies in cardiomyopathy is established, the precise identity of causative genes and their respective phenotypes in adult cardiomyopathy remains unclear.

Methods

We implemented a combination of echocardiography and whole exome sequencing in clinically diagnosed cardiomyopathy patients to uncover this relationship. This involved recording cardiac phenotypes, identifying genes associated with disrupted fatty acid metabolism, and subsequently followed up with these patients.

Results

Out of 802 cardiomyopathy patients, 27 exhibited mutations in genes tied to fatty acid metabolism. Specifically, 16 patients demonstrated a hypertrophic cardiomyopathy (HCM) phenotype, and 11 showed a dilated cardiomyopathy (DCM) phenotype. The implicated genes were SLC22A5 (n=7), ACADVL (n=6), ACADS (n=4), ACADM (n=3), SLC25A20 (n=3), ACADL (n=2), HADH (n=1), and AGK (n=1), with a higher prevalence in males. Among these, the SLC22A5 mutation was predominant and correlated with HCM phenotype. Notably, compound mutations were frequently observed (16/27), leading to earlier disease onset and diminished aortic sinus dimension. Further investigation showed that smaller aortic sinus dimensions resulted from abnormal left ventricular myocardial work. HCM phenotype mutation carriers showed more consistent left ventricular hypertrophy and a higher probability of right ventricular hypertrophy, while DCM phenotype mutation carriers exhibited impaired contractile function across all left ventricle segments. After a 24-month follow-up, the DCM phenotype group demonstrated higher cardiovascular risk, including two fatalities.

Conclusion

Our investigation highlights the significant prevalence of mutations related to abnormal fatty acid metabolism in adult cardiomyopathy patients, underscoring the utility of a gene-echocardiography approach for diagnosis.
Sex differences in RNA transcripts in dilated cardiomyopathy
Authors: Ljungman C , Jamialahmadi O , Bollano E , Anderson B , Romeo S , Bergh N
Published: October 2024

Introduction

Dilated cardiomyopathy (DCM) is the most common cardiomyopathy and a major cause of heart failure. Differences in clinical presentation and phenotype exist in men and women but the reason for this is not clear. The analysis of the RNA transcripts (mRNA sequencing) offers an opportunity to provide a link between the genome, the proteome, and the phenotype. The aim of this study was to explore sex differences using mRNA sequencing in patients with DCM.

Method

Our database, an observational prospective cohort study, includes patients referred for suspected cardiomyopathy. The database includes data on patients’ characteristics, symptoms, diagnostic procedures, treatments, cardiac devices, and outcome. Endomyocardial biopsy from the right ventricle was collected and total RNA, including miRNA and other small RNA, was isolated. RNA sequencing and library preparation was performed. Following quality check, reads were aligned to GRCh38 reference genome by STAR (v2.7.10a). Sex-specific differential expression analysis between individuals diagnosed with DCM (cases) versus non-confirmed cardiomyopathy (controls) was performed using DESeq2 (v.1.38.3) adjusting for age, RNA integrity number and systolic blood pressure. After controlling for multiple testing using the Benjamini-Hochberg method, genes with a corrected P-value < 0.05 were considered as being differentially expressed. Gene-set enrichment analysis on differentially expressed genes was performed via Enrichr tool using Descartes cell types and tissues, KEGG biological pathways, DisGeNET, and Gene Ontology Biological Processes (GOBP).

Results

Patients´characteristics in women and men with DCM is presented in table 1. There was no difference in outcome in men and women (data not shown). Differential expression analyses with transcriptomic data comparing DCM (n=43) versus controls (n=22) stratified by sex (DCM n= 9, (20.9%) women and controls n=7, (30.4%) women) was performed. There was no overlap between differentially expressed genes between sexes (Figure 1). In men gene set enrichment analyses showed that differentially expressed genes were related to pathways involved in dilated and hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (KEGG). Interestingly, these analyses revealed an enrichment of genes related to platelet biology, namely precursors (Descartes), activation (GOBP, KEGG) and platelet disorder (DisGeNET). In women, HLA-DQB1 was more expressed in DCM. HLA-DQB1 is associated with celiac disease, narcolepsy, and type 1 diabetes. Consistently, the enrichment analyses showed an enrichment of genes involved in autoimmune diseases (DisGeNET).

Conclusion

Women and men with DCM exhibit differently activated RNA transcripts although no difference in phenotype was observed. This may indicate that although DCM can be caused by similar factors in women and men the transcriptome is differently activated which warrants further investigation.Table 1.
Diagnosis of heart failure with preserved ejection fraction based on exercise stress echocardiography in real-world practice
Authors: Tani Y , Reddy Y R , Verbrugge F V , Yang J Y , Negishi K N , Harada T H , Saito Y S , Kagami K K , Yuasa N Y , Murakami F M , Sorimachi H S , Kato T K , Wada N W , Ishii H I , Obokata M O
Published: October 2024

Aims

The diagnostic difficulty of heart failure with preserved ejection fraction (HFpEF) is related to the fact that many patients develop abnormal hemodynamics only during exercise. Exercise stress echocardiography is a first-line test to unmask such abnormalities, but exercise protocols and diagnostic criteria have not been established. It remains unclear how cardiologists diagnose HFpEF by exercise echocardiography in real-world practice.

Methods and Results

An international web-based survey was performed on 87 cardiologists, 59% of whom had ≥ 6 years of experience with exercise echocardiography. A retrospective cohort of 652 dyspneic patients who underwent exercise echocardiography was used to determine the impact of different diagnostic criteria on the proportion of HFpEF diagnosis. The most commonly used exercise echocardiography criterion for the HFpEF diagnosis was the HFA-PEFF algorithm (48%), followed by the ASE/EACVI criteria (24%) and some combinations of multiple parameters (22%). A retrospective study found that the proportion of HFpEF diagnosis varied substantially between the criteria used: 20.1% for the ASE/EACVI criteria and 44.3% for the HFA-PEFF algorithm. A survey demonstrated that 54% of the participating cardiologists would initiate sodium-glucose co-transporter 2 inhibitors based on exercise echocardiography results.

Conclusion

In real-world practice, exercise echocardiography criteria for HFpEF diagnosis vary among cardiologists. While many cardiologists consider initiating pharmacological treatment on exercise echocardiography results, the frequency of HFpEF diagnosis varies substantially depending on the diagnostic criteria used. The lack of universal diagnostic criteria may limit the delivery of evidence-based treatment to patients with HFpEF.
Echocardiographic predictors of cardiovascular outcome in heart failure with preserved ejection fraction
Authors: Wang N , Rueter P , Hibbert T , Ng M , Chandramohan S , Osullivan J , Kaye D , Lal S
Published: October 2024

Background

The optimal echocardiographic predictors of cardiovascular outcome in heart failure with presereved ejection fraction (HFpEF) are unknown.

Purpose

We aimed to identify independent echocardiographic predictors of cardiovascular outcome in patients with HFpEF.

Methods

Systematic literature search of three electronic databases was conducted from date of inception until November 2022. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for echocardiographic variables from multivariate prediction models for the composite primary endpoint of cardiovascular death and heart failure (HF) hospitalization were pooled using a random effects meta-analysis. Specific subgroup analyses were conducted for studies that enrolled patients with acute versus chronic HF, and for those studies that included E/e’, pulmonary artery systolic pressure (PASP), renal function, natriuretic peptides and diuretic use in multivariate models.

Results

Forty-six studies totalling 20,056 patients with HFpEF were included. Three echocardiographic parameters emerged as independent predictors in all subgroup analyses: Decreased left ventricular (LV) global longitudinal strain (HR 1.24, 95% CI 1.10-1.39 per 5% decrease), decreased left atrial (LA) reservoir strain (HR 1.30, 95% CI 1.13-1.1.50 per 5% decrease) and lower tricuspid annular plane systolic excursion (TAPSE) to PASP ratio (HR 1.17, 95% CI 1.07-1.25) per 0.1 unit decrease). Other independent echocardiographic predictors of the primary endpoint were a higher E/e’, moderate to severe tricuspid regurgitation, LV mass index and LA ejection fraction, although these variables were less robust.

Conclusion

Impaired LV global longitudinal strain, lower LA reservoir strain and lower TAPSE/PASP ratio predict cardiovascular death and HF hospitalization in HFpEF and are independent of filling pressures, clinical characteristics and natriuretic peptides. These echocardiographic parameters reflect key functional changes in HFpEF, and should be incorporated in future prospective risk prediction models.
Cardiovascular risks of PD1 inhibitor therapy in cancer: impact of prior ischemic events on heart failure - a retrospective cohort study
Authors: Drobni Z , Gergely T , Zlotoff D , Gilman H K , Gong J , Wu J , Ghamari A , Merkely B , Reynolds K , Varga Z , Neilan T
Published: October 2024

Introduction

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, but concerns remain about their cardiac risks. Limited recent basic evidence suggests a possible link between ICIs that target PD1 and adverse cardiac events such as heart failure.

Purpose

This study explores the connection between PD1 inhibitor therapy and incident heart failure in cancer patients.

Methods

In our retrospective study at a tertiary medical center, 1,671 cancer patients receiving PD1 inhibitors were analyzed. Individuals with a history of heart failure, who developed myocarditis on PD-1, or had missing data were excluded. Data from pharmacy records and the Research Patient Data Registry provided clinical and ICI-related details. Cases were defined as patients who developed incident heart failure after ICI started. Controls were patients who did not develop incident heart failure after ICI start. Sensitivity analyses, including propensity score matching and comparison with non-ICI-treated cancer patients, ensured result robustness. Multivariate logistic regressions were performed.

Results

Among 1,671 ICI treated patients, 109 (6.5%) developed heart failure without evidence of myocarditis over a median follow-up of 332.0 days. In both the full cohort and the 3:1 matched cohort (n=380), multivariate logistic regression showed increased odds of incident heart failure in patients with prior ischemic cardiac events: 2.34 (95%CI 1.26-4.16, p=0.005) and 2.11 (95%CI 1.05-4.2, p=0.033) respectively. Among the non-ICI treated cancer patients, multivariate logistic regression found no association between prior ischemic events and incident heart failure (1.23, 95%CI 0.53-2.63, p=0.6), but hypertension showed an association (1.74, 95%CI 1.07-2.87, p=0.027).

Conclusion

This study emphasizes vigilance for cardiovascular complications in PD1 inhibitor-treated cancer patients. The incidence of heart failure was 6.5% over a follow-up period of less than 1 year. Prior ischemic events correlate with increased heart failure risk, suggesting a need for nuanced patient management. Understanding ICIs' cardiovascular safety is crucial for risk assessment, treatment optimization, and patient well-being.
Beyond resting measurements: exercise pulse pressure and its association with heart failure hospitalization
Authors: Fu Y , Huang W M , Sung S H
Published: October 2024

Background

Pulse pressure (PP), the difference between systolic and diastolic blood pressure, is a known predictor of heart failure (HF). While high resting PP has been linked to increased HF risk, the implications of exercise-induced PP changes remain less understood. This study investigates the contrasting roles of exercise PP in predicting hospitalization for heart failure (hHF).

Methods

We conducted a retrospective analysis of adults referred for treadmill exercise testing between 2003 and 2012. ΔMaximal BP referred to the BP change from rest to peak exercise. Cox proportional hazards models adjusted for demographic and clinical variables were used to assess the predictive value of PP changes for hHF.

Results

Among 15,249 participants, 117 (0.7%) were hospitalized for HF over a median follow-up of 112 months. Higher resting PP was significantly associated with an increased risk of hHF, whereas increased Exercise PP was inversely related to hHF risk independently (adjusted HR: 0.76, 95% CI: 0.67-0.86, P<0.001).

Conclusions

Resting PP and Exercise PP exhibit opposite effects on the risk of heart failure hospitalization. These findings suggest the importance of considering both resting and exercise-induced PP changes in the assessment and management of heart failure risk.
Clinical utility of fibrosis-4 index in predicting increased right atrial pressure
Authors: Jinno S , Yamada A , Izawa H
Published: October 2024

Introduction

Fibrosis-4 (FIB-4) index, derived from serum aspartate transaminase, alanine aminotransferase, platelet count and age, is an easily measurable marker reflecting hepatic fibrosis. Recently, FIB-4 index has been reported to be associated with cardiac events in heart failure (HF) patients. We examined whether FIB-4 index was useful in predicting elevated right atrial pressure (RAP) in comparison with directly measured RAP.

Methods

We studied consecutive 293 HF patients who underwent right heart catheter (RHC) examinations at our institution between Sep 2021 and May 2023. The exclusion criteria were as follows: viral or metabolic chronic hepatic diseases, thrombocytopenia. The subjects received RHC examination and blood test on the same day, and echocardiography within 3 days from the RHC examination. On top of FIB-4 index, diameter of inferior vena cava (IVC) and its respiratory changes were measured as a conventional method to estimate RAP.

Results

A total of 252 patients (mean 64.7 years of age, 52.8% men) were eligible for this study. FIB-4 index was significantly correlated with mean RAP (r = 0.39, p < 0.001). ROC curve analysis revealed that 1.80 was the optimal cutoff value of FIB-4 index to predict increased RAP > 10mmHg (AUC 0.74, p < 0.001, sensitivity 76.1%, specificity 74.0%). As shown in Figure, the diagnostic accuracy increased when FIB-4 index was combined with IVC diameter (AUC 0.77), which was significantly higher than the combination (AUC 0.71) of IVC diameter alone (AUC 0.71, p < 0.001, cutoff 17mm, sensitivity 67.6%, specificity 71.8%) and IVC respiratory changes alone (AUC 0.61, p = 0.005, cutoff 53%, sensitivity 77.5%, specificity 44.2%).

Conclusions

FIB-4 index was clinically useful in predicting increased RAP, especially when it was combined with IVC diameter.
Right ventricular myocardial work in heart failure with preserved ejection fraction: insights from invasive cardiopulmonary exercise testing
Authors: Lin T , Huang K C H , Chang K C C , Wu C K W
Published: October 2024

Backgrounds

Symptoms of heart failure with preserved ejection fraction (HFpEF) is closely related to elevated pulmonary capillary wedge pressure (PCWP) during exercise. The understanding of right ventricle myocardial work, assessing of right ventricular (RV) function utilizing RV pressure–strain loops, in HFpEF is lacking.

Methods

The study population underwent invasive cardiopulmonary exercise tests, measuring pressures at rest and during exercise to identify HFpEF. Echocardiography assessed LV and RV parameters. Right ventricular myocardial work was calculated using strain-rate and pressure curves, matching them with ECG data. RV global constructive work (RVGCW), RV global work index (RVGWI), RV global wasted work (RVGWW), and RV global work efficiency (RVGWE) were analysed and compared with invasively measured PCWP at resting and peak exercise.

Results

Between November 2017 and July 2023, 41 patients with adequate data were enrolled, and 21 were diagnosed with HFpEF. There were no significant differences in various echocardiographic parameters between HFpEF and non-HFpEF groups, except higher post-exercise PCWP and mean pulmonary artery pressure. HFpEF patients had higher RVGWW and lower RVGWE. RVGWW and RVGWE had higher predictive ability for HFpEF diagnosis compared to other echocardiographic parameters. While RVGCW (r = 0.0.504, P = 0.001 and r = 0.430, P = 0.006, respectively) and RVGWW correlated (r = 0.408, P = 0.008 and r = 0.621, P <0.001, respectively) with post-exercise ∆PCWP and exercise PCWP, only RVGWW (β=1.981, P=0.044 and β=4.323, p<0.001) being independently associated with both after adjustment for confounding factors.

Conclusions

RVGWW is a novel parameter that provides an integrative analysis of RV systolic function and correlates more closely with post-exercise ∆PCWP than other standard echocardiographic parameters in HFpEF.