bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of aortic valve function in over 47,000 people using deep learning
Authors: Kany S , Ramo J , Hou C , Jurgens S , Nauffal V , Cunningham J , Lau E , Butte A , Ho J , Olgin J , Elmariah S , Lindsay M , Ellinor P , Pirruccello J P
Published: November 2023

Background

Aortic valve (AV) stenosis (AS) is associated with a high global burden of mortality and morbidity. Previous studies suggest that even mild AS is associated with worse outcomes, prompting interest in AV function in a healthy population. The UK Biobank is a prospective cohort study with ∼500,000 participants of whom ∼10% have undergone cardiovascular MRI (cMRI).

Purpose

We aimed to develop a deep learning model to study AV function in cMRI at population level in the UK Biobank.

Methods and Results

We developed a U-Net based segmentation model with a ResNet34 encoder to study the velocity-encoded image series, computing peak velocity (cm/sec), mean peak gradient ("mean gradient"; mmHg), and aortic valve area (cm2) (AVA) in 47,223 participants.

Next, we calculated reference values stratified by age and sex in participants without CVD. In healthy individuals (n=31,909), AVA was lower in older age groups, whereas peak velocity and mean gradient remained similar across age groups. Compared to women, men had greater AVA but similar peak velocity and mean gradient estimates.

In the biomarker analysis (taken ∼9.5 years before cMRI), we observed an association of apolipoprotein B (ApoB) (0.033 SD increase per SD, P=3.1×10-12) and lipoprotein a (Lp (a)) (0.027 SD increase, P=4.8×10-07) with higher peak velocity. Using Mendelian Randomization, we found genetic evidence that Lp(a) causally contributes to higher peak velocity (β=0.04, P=6.4 × 10-10) and smaller AVA (β=-0.056, P=1.3 × 10-4). Similarly, ApoB causally contributes to higher peak velocity (β=0.072, P=1.3 × 10-6) and smaller AVA (β=-0.065, P=1.3 × 10-5) in Mendelian Randomization.

Peak velocity was strongly associated with incident AV surgery (N=72, Hazard ratio [HR] 2.40 per SD, P=2.6×10-110) and AS (N=123, HR 2.10, P=7.7×10-138). The predictive power for AS was higher when using the top 10% vs the remaining 90% of distribution for mean gradient (N in top 10% with event=87, HR 24.91, P=2.4×10-43) and peak velocity (N=92, HR 33.01, P=3.0×10-43). After excluding individuals with at least mild aortic stenosis (peak velocity > 2m/sec, mean gradient >20mmHg, AVA >1.5 cm2) the top 10% of the remaining population was still highly predictive for AS using mean gradient (N=30, HR 8.90, P=9.4×10-15) and peak velocity (N=35, HR 13.15, P=1.6×10-18).

Conclusion

We found both epidemiological and causal genetic evidence that elevated ApoB and Lp(a) cause a reduction in AVA. Even aortic velocities below the threshold for mild AS were predictive of future clinical disease, suggesting that there may be a role for monitoring at AVA below the current threshold for mild AS. Future work is needed to understand whether clinical outcomes are better predicted by universal or sex-specific cutoffs.Figure 1:Workflow of deep learning modeHR of incident valvular disease
Time of day dependent symptom onset is not associated with left ventricular function and myocardial damage after ST-segment elevation myocardial infarction
Authors: Holzknecht M , Lechner I , Reindl M , Tiller C , Fink P , Oberhollenzer F , Troger F , Mayr A , Bauer A , Reinstadler S J , Metzler B
Published: November 2023

Background

Circadian processes are suggested to influence ischemic injury in ST-segment elevation myocardial infarction (STEMI). Observational data suspect a circadian dependence of the occurrence of microvascular obstruction (MVO) in patients with STEMI. However, these observations derive from a small sample size and circadian variations in left ventricular function and myocardial damage after STEMI are still a matter of controversy.

Purpose

We aimed to investigate the association of time of day dependent symptom onset with left ventricular ejection fraction (LVEF), infarct size (IS) and MVO in a large cohort of STEMI patients treated with primary percutaneous coronary intervention (PCI).

Methods

This observational study investigated acute STEMI patients treated with primary PCI. Cardiac magnetic resonance (CMR) imaging was performed within 1 week after the index event for the determination of left ventricular function and infarct characteristics. The time of symptom onset was used to discriminate patients according to LVEF, IS as well as MVO occurrence and extent over a 24 hours cycle to evaluate circadian behavior.

Results

In final analysis, 889 acute STEMI patients treated with primary PCI with a delay of 189 [120-315] minutes were included. Median age of the overall cohort was 57 [51-66] years and 17% were female. Median LVEF was 49 [42-55]%, IS assumed 15.5 [8.0-24.7]% of left ventricular myocardial mass (LVMM) and MVO occurred in 57% of STEMI patients. No hourly differences between symptom onset and MVO occurrence (p=0.108), MVO extent (p=0.735), LVEF (p=0.644) and IS (p=0.722) have been evaluated. When comparing 3 hourly segments of symptom onset, no variations in MVO occurrence (p=0.114), MVO extent (p=0.308), LVEF (p=0.547) and IS (p=0.405) were observed.

Conclusions

No circadian variations in symptom onset and the occurrence and extent of MVO, LVEF and IS were observed in this large cohort of STEMI patients treated with primary PCI. Further research is needed to investigate the complex interplay between circadian processes and ischemic injury in this patient population.
Mitral annulus disjunction: a detailed magnetic resonance study of phenotype and clinical significance
Authors: Custodio P M , Campos P , Moura A R , Khanji M , Bicho J A , Lopes L R
Published: November 2023

Background

The clinical significance and arrhythmogenic propensity of mitral annulus disjunction (MAD) are not well established. Our aim was to characterize MAD in all-comers, analyzing the mitral valve apparatus in detail, scar burden and clinical outcomes.

Methods

Single-center retrospective analysis of all consecutive patients with MAD described by cardiovascular magnetic resonance (CMR) between 2010-2022. Medical history, imaging and arrhythmia data were analysed. Cardiovascular mortality was assessed. MAD was defined as a separation ≥2mm between the left ventricular myocardium and the mitral annulus. Presence and pattern of left ventricle (LV) late gadolinium enhancement (LGE) was assessed. Scar in the papillary muscles and areas adjacent to the MAD was identified as MAD-related. Ventricular arrhythmias (VA) were grouped into non-sustained (ectopies>10%/24h or ventricular tachycardia) or sustained.

Results

Out of 341 patients who were initially identified as possibly having MAD, MAD was confirmed in 222. Mean age was 49.2±19.3 years, 126 were male (56.8%). Mean longitudinal MAD extent was 5±2.6mm, while circumferential involvement of a single segment (60º) was most commonly seen (n=99, 44.6%). The inferior wall was the affected segment (n=116, 52.2%) with more extensive MAD, followed by the inferolateral wall (n=71, 32%). Mitral valve (MV) annulus expanded during systole in patients with MAD ≥6mm, while annular contraction occurred in those with MAD <6mm. Annular expansion was associated with MV prolapse (p=0.003), billowing (p=0.018) and curling (p<0.001). LV LGE was present in 82 patients (36.9%), with 23 patients (10.4%) showing MAD-related LGE, but no association with disease extent (MAD length or circumferential involvement). Median follow-up time was 1392 (872-1922) days. No episode of sustained VA was observed. In univariable analysis non-sustained VA was significantly more prevalent in patients with MAD ≥6mm (p=0.002), although this tendency faded after multivariate analysis (p=0.053). The presence of non-sustained VA was associated with global LV LGE (p=0.005), but not MAD-related LGE in isolation - Table 1. Three patients died of cardiovascular causes (1.4%), but none had extensive MAD or MAD-related LGE. None died of sudden cardiac arrest.

To the best of our knowledge, this is the biggest dataset of MAD patients that simultaneously analysis phenotype, including LGE, and clinical outcomes.

Conclusion

Mitral valve dysfunction (prolapse/billowing) is linked to MAD severity. Scar is common, not related to the extent of MAD, but a predictor of VAs independently of its location. The risk of sustained ventricular arrhythmias and cardiovascular death appears to be low in this all-comers population.Table 1
Atrial functional tricuspid regurgitation in patients undergoing transcatheter aortic valve replacement
Authors: Loew K , Steffen J , Lux M , Haum M , Fischer J , Orban M , Theiss H , Braun D , Massberg S , Hausleiter J , Deseive S
Published: November 2023

Introduction

Recently, a novel entity of tricuspid regurgitation (TR) – atrial functional TR, which is caused by enlargement of the right atrium – has gained in awareness. In comparison, ventricular functional TR occurs in the setting of left heart disease with pulmonary hypertension and subsequent enlargement of the right ventricle. While it could be demonstrated that in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), an improvement of moderate or severe tricuspid regurgitation (TR) can be observed in many patients, knowledge about the association between entity and improvement of TR is scarce.

Purpose

The aim of this study was to analyse if atrial functional TR, defined by the enlargement of the right atrium is associated with the persistence of TR after TAVR in patients with severe AS and at least moderate concomitant TR at baseline. Moreover, 3-year all-cause mortality in patients with atrial and ventricular TR was assessed.

Methods

We retrospectively examined 363 patients with at least moderate tricuspid regurgitation undergoing TAVR from January 2013 to December 2020 due to severe AS. Patients with primary TR, a history of tricuspid valve surgery or with TAVR due to severe aortic regurgitation were excluded. Endsystolic area of the right atrium (RA) and enddiastolic area of the right ventricle (RV) were assessed in transthoracic echocardiography and atrial TR was defined as RA/RV area ratio above the median value of 1.125.

Results

TR improvement of at least one grade after transcatheter aortic valve replacement was significantly less frequent in patients with atrial compared to patients with ventricular TR (29.2% vs. 60.3%, p < 0.001, Figure 1). Multivariate logistic regression analysis with adjustment for left ventricular ejection fraction, Vena contracta and CT-determined tricuspid annulus diameter confirmed that atrial functional TR was an independent predictor for absence of TR improvement after TAVR (adjusted odds ratio: 3.03, 95% CI 1.65-5.64; p<0.001). Moreover, improvement of TR was associated with a significantly lower 3-year all-cause mortality compared to patients with persistence of TR (log rank test p<0.001, Figure 2A). However, no difference could be observed regarding 3-year all-cause mortality between patients with atrial and ventricular TR (log-rank test p=0.500, Figure 2B).

Conclusion

In patients undergoing TAVR for severe AS and at least moderate concomitant TR, atrial functional TR is an independent predictor for TR persistence. In addition, TR persistence is associated with increased 3-year all-cause mortality.Figure 1:Development of TR after TAVRFigure 2:3-year all-cause mortality
Echocardiographic features predict the performance of transthoracic echocardiography in ruling out infective endocarditis: a 5-year study
Authors: Zhang R Y K , Litkouhi P N , Ramanayake A , Youssef G
Published: November 2023

Background

Transoesophageal echocardiography (TOE) remains the gold standard imaging modality to aid in the diagnosis of infective endocarditis (IE), but is resource intensive and confers patient risk. Transthoracic echocardiography (TTE) is a more accessible alternative, but previous studies report varying ability of TTE to effectively rule out disease. As a result, negative TTE is often still followed with TOE when clinical suspicion remains. However, these studies did not account for TTE quality and other echocardiographic features within the TTE that may decrease its diagnostic utility and thereby reduce its ability to effectively rule out disease. Understanding the risk of missing IE for a given negative TTE could avoid the need for subsequent TOE.

Purpose

Our aim is to devise and test the validity of a scoring system which can stratify TTEs by quality to predict TTE performance and inform the decision for whether follow-up TOE is necessary.

Methods

In this retrospective single-centre study, the Predictor of TTE Performance (PTP) scoring system was developed and applied to patients undergoing both TTE and TOE for suspected IE at our tertiary centre between May 2017 and May 2022. Within the scoring system, a point was allocated for the presence of each of the following on TTE: a mobile echodensity; poor image quality; more than mild regurgitation; a prosthetic valve or prosthetic intracardiac material; and other valvular abnormalities. Poor image quality was defined as any TTE that was unable to achieve good endocardial visualisation from at least two views. Valvular abnormalities warranting a point included congenital abnormalities such as bicuspid aortic valve and acquired abnormalities such as rheumatic valvular disease, mitral valve prolapse and valvular stenosis. The negative predictive value (NPV) for TTEs in each score category was analysed using TOE as the gold standard.

Results

A total of 362 patients with paired TTE/TOE were included for analysis. 60 (16.6%) had positive TOE, with the overall NPV of TTE being 88.5% (95% CI: 84.6–91.5%). Using the PTP scoring system, patients were stratified into low-risk (score of 0, n = 116), moderate-risk (score of 1, n = 140) and high-risk (score greater than 1, n = 106) groups. Increasing PTP score was associated with poorer TTE performance, with the low-risk, moderate-risk and high-risk categories having NPVs of 98.3% (95% CI: 93.9–99.7%), 90.2% (95% CI: 83.9–94.2%) and 72.3% (95% CI: 61.8–80.8%) respectively.

Conclusion

The ability of TTE to exclude IE is excellent when patients have no echocardiographic features that reduce TTE quality or predict increased risk for endocarditis. In patients with a low PTP score, negative TTE may render follow-up TOE unnecessary.
One-year outcome of elderly patients with endocarditis: a retrospective observational study
Authors: Marchini F , Zanarelli L , Bianchi N , Tonet E , Passarini G , Guardigli G , Campo G , Pavasini R
Published: November 2023

Background

The incidence of infective endocarditis (IE) is rising in general population, especially in elderly, where it is associated with high morbidity and mortality. Health care procedures, degenerative heart valve diseases and intracardiac electronic devices are the main risk factors for IE in elderly population. Cardiac surgery is largely underused in these patients and the few available observational studies seem to confirm the positive outcome of surgery.

Purpose

The aim of the present study is to assess differences in survival between elderly patients affected by endocarditis treated with a conservative strategy or cardiac surgery.

Methods

We conducted a retrospective observational study of 143 elderly patients (age ≥ 70 years old) affected by endocarditis with at least one year of follow-up who were hospitalized between 2016 and 2022. The primary endpoint was the difference in one-year all-cause mortality between patients treated with a conservative strategy or cardiac surgery. The secondary endpoint was one-year mortality for sepsis or septic shock. The cumulative probability of survival was calculated using the Kaplan-Meier estimator. The log-rank test was used to compare between-group differences in survival and cox regression was used in the uni and multivariate analysis, a p<0.05 was considered significant.

Results

Between 2016 and 2022, 242 patients have been diagnosed with IE. Between them, 143 patients were at least 70 years old (59%). Cardiac surgery was performed in 16 patients, while 127 were treated with medical therapy alone. Patients treated with cardiac surgery were younger (74y vs 80y, p=0.005) and had higher prevalence of severe valvular heart disease (69% vs 23%, p< 0.001). The primary endpoint of one-year all-cause mortality occurred in 80 patients in the conservative strategy group and in 5 patients treated with surgery (p=0.015); the secondary endpoint occurred in 42 patients in conservative strategy group, while no patients treated with surgery died for sepsis or septic shock (p=0.006). Finally, surgery was associated with better one-year survival (HR 0.34, 95% CI 0.14 - 0.85).

Conclusions

IE in elderly patients is an emerging clinical matter since its incidence is rising but mortality has not significantly decreased. Current clinical guidelines do not give specific indication for elderly, who are generally excluded from surgery due to the high risk carried by age and comorbidities. Few previous studies have analyzed the best treatment strategy in this cohort of patients, but data from observational studies shows a better outcome among those undergone surgery. The result of our work confirmed that elderly patients with IE treated with cardiac surgery have better one-year survival and lower rate of death for all causes, sepsis or septic shockKaplan Mayer Curve For One-Year Survival
Meta-analysis of the performances of contemporary risk models in cardiac surgery for infective endocarditis
Authors: Wang T K M , Agrawal A , Arockiam A D , El Dahdah J , Honnekeri B , Shekhar S , Unai S , Griffin B
Published: November 2023

Background

Risk scores play important roles in the decision-making for cardiac surgery, but remain under-studied in the setting of infective endocarditis (IE) when there is often a high risk of adverse outcomes. Several IE-specific risk scores have been developed recently, but there is a paucity of external validation studies. We aimed to pool the performance of current risk models applied to IE surgery.

Methods

Ovid Medline, Ovid Embase and Cochrane Library were comprehensively searched following PRISMA guidelines for eligible studies. Standard meta-analysis techniques using random effects models were used to pool the discriminative and calibration performance of risk scores for predicting operative mortality after IE surgery.

Results

Amongst 620 studies and 50 full-text articles screened, 17 studies reporting 12 risk scores and totaling 6337 patients were included. Amongst traditional risk scores, EuroSCORE I, EuroSCORE II, and STS IE score had pooled areas under curve (95%CI) of 0.727 (0.700.754), 0.753 (0.731-0.775), and 0.695 (0.645-0.746) (Table1). However, EuroSCORE II significantly over-estimated operative mortality while EuroSCORE I had good calibration with pooled Peto’s odds ratio (95%CI) of 2.47 (1.22-5.01) and 1.00 (0.74-1.36) respectively. Amongst IE-specific scores, areas under curve (95%CI) was highest for the ANCLA score 0.838 (0.803-0.873) and lowest for the COSTA score 0.641 (0.573-0.710).

Conclusion

Most contemporary risk score had moderate discriminative ability for operative mortality after IE surgery, with the IE-specific ANCLA score performing the best. However, there is room for improving the performance of current risk models, along with need for further external validation studies and calibration assessment, especially for IE-specific scores.
Prevalence, profile, causes and prognostic factors of surgical rejection in patients with left-sided infective endocarditis
Authors: Lopez Diaz J , De Miguel M , Pulido P , Cabezon G , Lozano A , Vilacosta I , Olmos C , Saez C , Gomez I , San Roman J A
Published: November 2023

Background

Despite the benefits of cardiac surgery in infective endocarditis, a high proportion of patients with surgical indication are not operated, which worsens their prognosis profoundly. Several attempts have been done to study this group of patients, but many aspects remain unclear so far.

Purpose

To analyze the prevalence, to describe in detail their characteristics, to determine the reasons for the denial and the prognostic factors of these patients in the widest series to date of patients with surgical indication but not operated.

Patients and methods

We included in an ongoing multipurpose database, all patients with definite left-sided infective endocarditis admitted in three Spanish tertiary hospitals from 2005 to 2022. We describe the clinical, epidemiological, microbiological, echocardiographic characteristics of patients with surgical indication according to the European guidelines who did not undergo surgery and compared with those patients operated on. We also analyzed the reasons of the denial and finally, through a univariate and multivariate analysis, determine the independent factors of in-hospital mortality of these patients.

Results

Of a total of 1105 patients with left-sided infective endocarditis of our series, 893 had surgical indication (81%) and 219 did not undergo surgery (19.8%). The main reason for surgical rejection was very high risk determined by an endocarditis team (56%), followed by stroke (25%), death before surgery (15%) and patient rejection (0.7%). The most frequent surgical indication of patients who were not operated was uncontrolled infection (50.4%). Patients not operated were older (73 vs 63; p<0.001), more frequently female (38.8% vs 29.5%; p=0.01), diabetic (34.7% vs 24.4%, p=0.003) and chronic renal failure (27.4% vs 11.3%; p<0.001). At admission they had more stroke (21.5% vs 12.1%; p=0.001) and septic shock (13.2% vs 6.9%; p=0.03). Staphylococcus aureus (34.7% vs 16.5%; p<0.001) and echocardiographic vegetations (92.7% vs 85.3%; p=0.005) were more frequent whereas Streptococcus viridans (8.2% vs 17.7%; p=0.001) and severe valvular regurgitation (64.8% vs 74.6%; p=0.005) were less frequent. In hospital mortality of patients not operated was 63.9%, significantly higher than operated patients (23%; p<0.001). The only independent risk factor of in-hospital mortality in patients with surgical indication who did not undergo surgery was persistent infection (HR 3.689; CI 95% 1.75-7.78).

Conclusions

A very high proportion of patients with definite left-sided infective endocarditis had surgical indication according to the European guidelines, but a quarter of them were not operated. Very high surgical risk was the main reason for the denial. They were older, had more comorbidities and a more aggressive microbiological profile. Mortality of these patients was three times higher than operated patients.
Association of dysglycaemia with persistent infarct core iron in patients with acute ST-segment elevation myocardial infarction
Authors: Oberhollenzer F , Lechner I , Reindl M , Tiller C , Holzknecht M , Fink P , Mayr A , Bauer A , Reinstadler S , Metzler B
Published: November 2023

Background

Dysglycaemia increases the risk of myocardial infarction and subsequent recurrent cardiovascular events. However, the role of dysglycaemia in ischemia/reperfusion injury with development of irreversible myocardial tissue alterations remains poorly understood.

Objectives

To investigate the association of dysglycaemia with persistence of infarct core iron and their longitudinal changes over time in patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI).

Methods

We analyzed 348 STEMI patients treated with primary PCI between 2016 and 2021 that were included in a prospective observational study. Peripheral venous blood samples for glucose and glycated hemoglobin (HbA1c) measurements were drawn on admission and 4 months after STEMI. Cardiac magnetic resonance (CMR) imaging including T2* mapping for infarct core iron assessment was performed at both time points. Associations of dysglycaemia with persistent infarct core iron and iron resolution at 4 months were calculated using multivariable regression analysis.

Results

Persistent infarct core iron was present in 89 (26%) patients (HBA1c <5.7%: 16%, 5.7-6.4: 37%, ≥6.5: 34%) and was independently associated with HbA1c levels (OR: 1.64 [95% CI: 1.11-2.42]; p=0.01), but not glucose levels on admission. The independent association was present even after exclusion of patients with diabetes (pre- and newly diagnosed, n=42). Infarct core iron resolution was observed in 34 (14%) patients and was independently associated with HbA1c levels at 4 months (OR: 0.51 [95% CI: 0.28-0.93]; p=0.03).

Conclusions

In STEMI patients treated with primary PCI, dysglycaemia is independently associated with persistent infarct core iron and impaired iron resolution at 4 months. Persistent infarct core iron might represent a mechanistic driver for adverse outcome and a potential therapeutic target in patients with altered glycemic status suffering acute STEMI.
Prognostic value of left ventricular hypertrophy in patients with myocardial fibrosis by ECV mapping on cardiac MRI
Authors: Alam L , Riasat M , Reyes H , Lopez P , Kim G H , Elias J , Argulian E , Agarwal V
Published: November 2023

Background

Cardiovascular magnetic resonance (CMR) can noninvasively identify myocardial fibrosis using extracellular volume (ECV) mapping. In patients with elevated ECV, and without hypertrophic cardiomyopathy (HCM) or cardiac amyloidosis, the prognostic significant of mild-to-moderate left ventricular hypertrophy (LVH) has not been well established.

Purpose

To determine if the presence of mild to moderate LVH has an impact on major adverse cardiovascular outcomes (MACE) in patients with elevated ECV without HCM or cardiac amyloidosis.

Methods

This was a retrospective cohort study assessing a group of patients referred for CMR between July 2019 and January 2023 to Mount Sinai Morningside. Patients with ECV>30% and left ventricular wall thickness <1.6 cm (to exclude patients with the possible diagnosis of HCM or cardiac amyloidosis) were considered for inclusion. Those with an established diagnosis of HCM or cardiac amyloidosis were also excluded. The LVH group comprised of patients with mild-to-moderate LVH, defined as a maximum wall thickness of 1.2-1.5 cm. The control group included patients without LVH (wall thickness <1.2 cm). Patients were further stratified by ECV, using the median value for our sample, as "high ECV" (≥35%) or "low ECV" (<35%). The outcome of interest was time-to-first MACE (all-cause death, or incident acute coronary syndrome, acute heart failure, or arrhythmia). Time-to-first MACE within 1 year was compared among groups using unadjusted Kaplan-Meier curves. Additional Cox regression analyses were performed to adjust for significant univariate analysis, including hypertension, hyperlipidemia, diabetes mellitus, use of beta-blocker, use of diuretic, and category of glomerular filtration rate. The results are presented as hazard ratios and 95% confidence intervals. All analyses were performed in SAS Enterprise using α<0.05.

Results

Out of the cohort, we identified 186 patients that met our selection criteria. The mean age was 61.1 ± 15.5 years, and 58.1% of patients were female. The median follow-up was 175 days in the control group and 115 days in the LVH group. There were 61 MACE (32.8%) in our sample. After adjusting for covariates, mild-to-moderate LVH was associated with 2.2 times the risk of MACE (95%CI 1.3 to 3.8; p=0.0047) at 1 year, compared to patients without LVH. A higher ECV (≥35%) was not significantly associated with worse outcomes within each study arm (p=0.3450). Kaplan Meier survival curves for patients with and without LVH are shown in Figure 1 (p=0.0002).

Conclusions

In patients with evidence of elevated ECV without underlying cardiac amyloidosis or hypertrophic cardiomyopathy, mild-to-moderate LVH is associated with 2.2 times the risk of MACE compared to normal left ventricular wall thickness.Figure 1
A novel strategy for key gene identification in hypertrophic cardiomyopathy based on cuproptosis and multiple WGCNA analyses
Authors: Xiao Y , Pan R J , An Z H , Liu Q M , Zhou S H
Published: November 2023

Background

Hypertrophic cardiomyopathy (HCM) is a potentially fatal disease, and early diagnosis is crucial for effective treatment. Microarray analysis and the discovery of cuproptosis, a new form of cell death, offer new possibilities for identifying potential biomarkers for early diagnosis.

Purpose

This study aimed to identify cuproptosis-related genes associated with HCM and potential biomarkers for early diagnosis using machine learning.

Methods

Expression data of cuproptosis-related genes were extracted from the GSE36961 dataset, and differential expression analysis was conducted. Immune infiltration analyses were also performed. Samples were categorized into two clusters, and cluster weighted gene coexpression network analysis (WGCNA) was performed based on HCM and cluster clinical data. The results were combined to develop the best machine learning model, which was verified through calibration and external validation (GSE1145 and GSE32453).

Results

Cuproptosis-related genes (NLRP3, ATP7B, ATP7A, SLC31A1, LIAS, LIPT1, DLD, DLAT, PDHB, and DBT) were differentially expressed between HCM and control samples. Five key genes (TSPAN12, ANP32C, C4ORF18, COL21A1, and HMGB2) were identified, which showed great efficiency in the diagnosis of HCM in external validation, with an AUC of 0.948. These genes may play critical roles in megakaryocyte differentiation, RAGE receptor binding, and protein digestion and absorption.

Conclusions

Cuproptosis-related genes may play significant roles in HCM, and TSPAN12, ANP32C, C4ORF18, COL21A1, and HMGB2 may be potential biomarkers for the early diagnosis of HCM. This study provides new insights for further research on HCM diagnosis and treatment.Flow chart of research designEvaluation and verification results
Perfomance of sudden cardiac death prediction strategies before and after Septal Reduction Strategies in patients with Hypertrophic Cardiomyopathy
Authors: Maurizi N , Fumagalli C , Ho C , Day S , Olivotto I
Published: November 2023

Background

Actual sudden death (SD) risk stratification strategies for Hypertrophic Cardiomyopathy have not been validated for patients after a septal reduction treatment (SRT). Therefore, it is largely unresolved the quantification of the ventricular arrhythmias (VA) burden after an SRT and how risk stratification should be performed in such patients.

Purpose

To evaluate the performance of ESC SD Risk stratification model and AHA ACC Risk Factors for SD in the identification of patients with lethal ventricular arrhythmias after SRT.

Methods

Data from 11 high-volume HCM specialty centers from the international SHaRe Registry were used to describe the natural history of patients with SRT. Patients were followed from SRT until last follow-up or meeting the composite outcome of ventricular arrhythmias (sudden cardiac death (SCD), resuscitated cardiac arrest, or appropriate implantable cardioverter-defibrillator (ICD) therapy). Cox proportional hazards models were used to identify predictors of prognosis and incident development. Calculation of SD score was performed before the SRT and at 1 year from the procedure.

Results

Of the 10385 patients part of the ShaRe Registry, 1835 (18%, 968 (53%) males) underwent a SRT during a median follow-up of 6.8 (IQR 3.4-9.8). A total of 455 (25%) had Alcohol Septal Ablation (ASA) and 1377 (75%) had myectomy. Patients who underwent myectomy were younger (49±18 vs 56±15 years, p<0.01), more frequent with a sarcomeric mutation (396 (29%) vs 111 (24%), p<0.01). Over 6.8 years after the procedure, 77 (4%) died because of HCM (0.6%/year) and 87 (5%) presented a composite VA outcome (0.7%/year). Development of the composite VA event was associated with younger age at procedure (38±20 vs 54±18 years, p<0.01), the development of a LV EF< 50% (29 (33%) vs 351 (20%), p<0.01), a more severely dilated LA (47±7 vs 43±11 years, p<0.01) and greater LV maximal wall thickness (24±6 vs 21±6 years, p<0.01). Significant predictor of the composite VA outcome was the presence of a LA diameter ³ 45 mm (HR, 2.6 [95% CI, 1.7–3.5]). Patients who presented the VA outocome were classified according to ESC SCD Risk pre and post SRT as: 40 (46%) as high risk, 31 (36%) as intermidiate risk, 16 (18%) as low risk pre intervention and 26 (46%) as high risk, 41 (47%) as intermidiate risk, 20 (18%) as low risk post procedure. AHA ACC SCD risk factors pre and post SRT classified patients as: 56 (64%) as class IIA 25 (29%) as Clas IIB, 6 (7%) as Class III and post SRT 42 (48%) as Class IIA, 31(36%) as Class IIB, 14 (16%) as Class III.

Conclusions

Current stratification strategies potentially underestimate the risk of SD pre and post SRT. Specifically, ESC SD risk strategies underperformed in the identification of intermidiate high risk patient, whereas AHA ACC were capable of identifying 84% of patients who had a malignant VA.
Sacubitril/valsartan for treatment of symptomatic non-obstructive hypertrophic cardiomyopathy: a randomised, controlled, phase II clinical trial (SILICOFCM)
Authors: Velicki L , Popovic D , Okwose N C , Preveden A , Tesic M , Tafelmeier M , Charman S J , Macgowan G A , Filipovic N , Ristic A , Olivotto I , Maier L S , Jakovljevic D G
Published: November 2023

Aim

To evaluate the effect of sacubitril/valsartan on exercise capacity, cardiac structure, and function in patients with hypertrophic cardiomyopathy (HCM).

Methods

Phase II, randomised, open-label multicentre study enrolled adult patients with symptomatic non-obstructive HCM (NYHA class I–III) who were randomly assigned (2:1) to receive sacubitril/valsartan (target dose 97/103mg) or usual care for 16 weeks. Primary endpoint was a change in peak oxygen consumption (peak VO2). Secondary endpoints included echocardiography measures of cardiac structure and function, natriuretic peptides and other biomarkers, and Minnesota Living with Heart Failure quality of life (QoL).

Results

Between May 2018 and November 2021, 354 patients were screened for eligibility, 115 patients (mean age 58 years [SD 11], 37% women) met the study inclusion criteria and were randomly assigned to sacubitril/valsartan (N=79) or usual care (N=36). At 16 weeks, there was no significant change in peak VO2 from baseline in sacubitril/valsartan (15.3 [4.3] vs 15.9 [4.3] ml/kg/min, p=0.13), or usual care group (p=0.47). There was a significant reduction in ventilatory efficiency slope (30.1 [7] vs 28.4 [4.9], p=0.03), but not in the control group (p=0.09). No significant changes were found in systolic or diastolic function, cardiac structure, or plasma biomarkers. The QoL score decreased significantly in the sacubitril/valsartan by 6 points (p=0.005) but not in the usual care group (p=0.66).

Conclusion

In patients with hypertrophic cardiomyopathy, 16 weeks of treatment with sacubitril/valsartan was well tolerated and contributed to a significant improvement in ventilatory efficiency and quality of life but not in exercise capacity or cardiac function.
Relation between non-sustained ventricular tachycardia and major arrhythmic events in patients with dilated cardiomyopathy caused by titin truncating variants
Authors: Hirose K , Cannie D , Syrris P , Bakalakos A , Elliott P
Published: November 2023

Background

Truncating titin variants (TTNtv) are the most frequent monogenetic cause of dilated cardiomyopathy (DCM). Current data suggest that nonsustained ventricular arrhythmia is common in patients with TTVtv but its relation to the risk of major arrhythmic events (MAE) is uncertain.

Purpose

To investigated the relationship between NSVT recorded on Holter ECG or implanted device and MAE in patients with DCM.

Methods

We retrospectively studied consecutively evaluated patients with DCM (left ventricle ejection fraction (LVEF) below 50%) on echocardiography and a pathogenic TTNtv. Patients with obstructive coronary artery disease, valvular disease, ventricular tachycardia ablation during follow-up time and follow-up less than one month were excluded. Survival was modelled from the initial Holter or device implantation. NSVT was defined as ≥3 consecutive ventricular beats at a rate >120 beats per minute, lasting for <30 s. MAE was defined as sustained ventricular tachycardia (VT), ventricular fibrillation (VF), sudden cardiac death, implantable cardioverter defibrillator (ICD) treated ventricular arrhythmias (appropriate shock and ATP). The clinical endpoint was MAE (sustained VT, VF, sudden cardiac death, ICD shocks and ATP) and multivariable analysis was performed using Cox proportional hazards models. Event-free survival probabilities were estimated using the Kaplan-Meier method, and comparisons of Kaplan-Meier curves were made using log-rank tests.

Results

The cohort comprised 58 men and 30 women [mean age 49 ± 15 years; mean follow-up 3.5 ± 1.8 years]. Symptoms were NYHA class I in 56 patients, class II in 25 patients, class III in 7 patients and class IV in none. Holter ECGs were performed in 77 patients, 41 of whom had NSVT. Twenty five patients had pacemaker/ICD in situ; 14 had NSVT. Six patients had MAE; 4 with NSVT. Univariate analysis association between MAE and LVEF ≤35% (hazard ratio (HR), 9.03; 95% confidence interval (CI), 1.49-54.71; P=0.017), prolonged (>8 beats) NSVT (HR, 6.71; 95% CI, 1.22-36.98; P=0.029) and fast (>200 bpm) NSVT (HR, 5.09; 95% CI, 1.02-25.47; P=0.048). Kaplan-Meier showed similar differences in freedom from MAE (LVEF ≤35%; P=0.004, long NSVT; P=0.025, fast NSVT; P=0.031).

Conclusion

Fast and prolonged NSVT is associated with a higher risk of MAE in patients with TTNtv.Characteristics at the beginningSurvival probability for freedom
Monitoring patisiran and inotersen treatment with quantitative SPECT/CT in hereditary transthyretin amyloid cardiomyopathy
Authors: Rettl R , Calabretta R , Duca F , Binder C , Kronberger C , Dona C , Beitzke D , Loewe C , Bonderman D , Hengstenberg C , Badr Eslam R , Kastner J , Bergler-Klein J , Hacker M , Kammerlander A A
Published: November 2023

Background

Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv).

Purpose

We aimed to determine treatment effects on myocardial amyloid load determined by quantitative single photon emission computed tomography/computed tomography (SPECT/CT) in patients with ATTRv-related cardiomyopathy (ATTRv-CM) and to identify nuclear imaging biomarkers to quantify and monitor response to therapy.

Methods

ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid ([99mTc]-DPD) scintigraphy and SPECT/CT imaging before and after 12 months of treatment with patisiran (n=5) or inotersen (n=4).

Results

Patisiran-treated patients had a significant reduction in cardiac uptake as measured by standardized uptake values (SUVpeak: 7.98 g/mL ±0.87 vs. 6.50 g/mL ±1.59, p=0.025, Figure 1A; SUVmax: 8.80 g/mL ±0.94 vs. 6.96 g/mL ±1.59, p=0.009, Figure 1B; SUVmean: 5.64 g/mL ±1.01 vs. 4.42 g/mL ±1.26, p=0.016, Figure 1C). Patients treated with inotersen showed evidence of stabilization in cardiac SUV uptake (SUVpeak: 8.56 g/mL ±2.25 vs. 7.99 g/mL ±1.90, p=0.665; SUVmax: 9.29 g/mL ±2.39 vs. 8.79 g/mL ±2.03, p=0.719; SUVmean: 5.07 g/mL ±1.46 vs. 4.86 g/mL ±0.95, p=0.834) but had significant deterioration in left ventricular (LV) function (LV cardiac index: 3.39 L/min/m2 ±0.04 vs. 2.94 L/min/m2 ±0.01, p=0.028, Figure 1D). Comparison of cardiac SUV uptake and longitudinal cardiac function revealed significant correlations between longitudinal changes in cardiac SUVpeak and LV global longitudinal strain (r=-0.658, p=0.027, Figure 1E) and right ventricular free wall longitudinal strain (r=-0.771, p=0.008, Figure 1F).

Conclusions

In conclusion, using serial quantitative SPECT/CT imaging, we demonstrated that patisiran treatment significantly reduces cardiac SUV uptake in ATTRv-CM patients, indicating regression of cardiac TTR amyloid. Our data suggest that quantitative SPECT/CT imaging may be a valid tool to quantify and monitor response to disease-specific RNAi therapeutic agents in ATTRv-CM patients.Figure 1Graphical Abstract
Temporal trends of clinical outcomes in patients hospitalized with acute pericarditis: analysis of the nationwide database in Japan
Authors: Aikawa H , Fujino M , Nakao K , Nakai M , Sumita Y , Miyamoto Y , Takagi K , Otsuka F , Kataoka Y , Asaumi Y , Tahara Y , Tsujita K , Noguchi T
Published: November 2023

Background

Most patients with acute pericarditis are considered to have a good prognosis, but the short-term outcomes and whether they improve or worsen over time are unknown in large clinical databases.

Purpose

We sought to investigate in-hospital mortality and incidence of cardiac tamponade in patients hospitalized for acute pericarditis in Japan, as well as trends over time in these outcomes.

Methods

From the Japanese Registry of All Cardiac and Vascular Diseases database from 2016 to 2020, we analyzed 7,374 patients hospitalized for acute pericarditis at 871 certificated hospitals by Japanese Circulation Society. We included etiology of acute pericarditis by idiopathic, connective-tissue disease, and post-cardiac injury syndrome. The primary and secondary outcome was in-hospital mortality and incidence of cardiac tamponade, respectively. Cochran-Armitage test was performed.

Results

In Japanese acute pericarditis patients (mean age; 65.0 years, male 71.0%), the etiology was idiopathic 96.2%, connective-tissue disease 2.1%, and post-cardiac injury syndrome 1.7%. The mortality rate and incidence of cardiac tamponade were 2.2% and 5.3%, respectively. Secular trend in those rates remained unchanged over time (p-trend = 0.30 and 0.19). The rates of mortality and cardiac tamponade were 2.1% and 5.2% in idiopathic pericarditis, 1.3% and 10.5% in connective-tissue disease, and 7.0% and 3.9% in post-cardiac injury syndrome, respectively. Connective-tissue disease pericarditis was at higher risk of cardiac tamponade compared to idiopathic pericarditis (5.2 vs. 10.5%, P=0.004). In addition, compared to idiopathic pericarditis, postoperative cardiac pericarditis tended to have a higher mortality rate (2.1 vs. 7.0%, P<0.001).

Conclusion

The short-term prognosis of acute pericarditis did not change significantly over time. This finding that clinical outcomes differed depending on the underlying disease suggests to clinicians the importance of differential diagnosis.
External validation of survival predicting score in repaired tetralogy of Fallot: an opportunity to improve
Authors: Ribeiro Teixeira A R , Barbas De Albuquerque F , Branco Mano T , Rito T , Antonio M , Laranjo S , Oliveira M , Cruz Ferreira R , De Sousa L
Published: November 2023

Introduction

In recent years, integrating both better diagnosis and treatment allowed most adults with repaired tetralogy of Fallot (rTOF) to expect a longer life expectancy. However, a minority is at higher risk for premature cardiovascular death. Recently, 2 scores identified the subgroup of rTOF patients (pts) who are at high annual risk of death and ventricular arrhytmias (VA). We aimed to implement both in our population.

Methods

Retrospective single center review was done on rTOF pts who undergone cardiovascular magnetic resonance with gadolinium, blood sampling for B-type natriuretic peptide (BNP), echocardiography and cardiopulmonary exercise testing. The risk scores were calculated with weighted independent predictors, namely presence of late gadolinium enhancement in left ventricle (LV) and right ventricle (RV), akinetic RV outflow length, LV and RV ejection fraction (EF), RV systolic pressure, peak oxygen uptake (pVO2), BNP, atrial arrythmias and age. Low mortality risk was defined as 0-20 points, intermediate as 21-50 and high ≥51. In terms of VA prediction, low risk was defined as 0-20 points, intermediate as 21-39 and high as ≥51.

Results

From a total of 240 rTOF pts, 61 (56% male, mean age 34±9 years) had all the necessary data. RV dysfunction was present in 52.5%, RV systolic pressure was high in 12 and LVEF≤35% in 18% pts. BNP level was elevated in 27 and pVO2≤17mL/kg/m2 in 14.8% pts. The mean mortality risk score was 15.1±11.2, being that 68.9% had a lower and 31.1% an intermediate risk. Regarding VA score, the mean was 14.7±10.8, where the majority (80.3%) were in lower risk. 29.5% had a sustain atrial arrhythmia (mainly atrial fibrillation) and 14.8% a VA. There were 3 cardiac related deaths (4.9%). Analysis of time to event data showed that mortality and VA scores were not predictors of overall mortality (M) or VA events, respectively. However, considering 1-year M, LVEF≤35% (p= 0.002), RVEF≤35% (p=0.002), pVO2≤17mL/kg/m2 (p<0.001), and both scores: M (p=0.013) and VA (p<0.001) were predictors of that endpoint. In multivariate analysis, VA risk score (p=0.035) and low pVO2 (p= 0.006) were independent 1-year M predictors.

Conclusion

In our population, ventricular arrhythmia score and low peak oxygen uptake were independent predictors of 1-year mortality. However, there is probably a selection bias. Since the scores were recently proposed, patients were not recruited prospectively, many ended up not having all the needed or recent data, thus were not included. There is the need to validate and improve available scores to truly assess the risk of mortality and arrhythmias, as well as defined protocols and longer follow-up for this purpose.