bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous Coronary Artery Dissection (SCAD) with cardiac arrest at presentation: a subanalysis from the DISCO registry
Authors: Giacobbe F , Bruno F , Brero M , Macaya F , Benenati S , De Filippo O , Chinaglia A , Escaned J , De Ferrari G M , Varbella F , Cerrato E , D'ascenzo F
Published: October 2024

Introduction

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (AMI), which primarily affects young women without traditional cardiovascular risk factors, often presenting as sudden cardiac death. This study aims to investigate the prevalence, characteristics, predictors, and outcomes of cardiac arrest in SCAD patients.

Methods

The DISCO IT/SPA registry, an international retrospective multicenter study, enrolled 375 SCAD patients from 26 centers in Italy and Spain. Patients were categorized based on the presence or absence of cardiac arrest at admission. Data on demographics, clinical presentation, treatment, angiographic findings, and outcomes were collected. Angiograms were independently reviewed, and outcomes included major adverse cardiovascular events (MACE) and in-hospital bleeding.

Results

Among 375 SCAD patients, 20 (5.3%) presented with cardiac arrest. Both groups were similar in age, gender distribution, and conventional risk factors, except for a lower prevalence of dyslipidemia in the cardiac arrest group. ST-segment elevation myocardial infarction (STEMI) presentation and angiographic type 2b were independent predictors of cardiac arrest. Revascularization was more frequent in the cardiac arrest group. In-hospital outcomes, except for longer hospitalization, did not differ. On follow-up (average 21 months), MACE rates were similar between groups.

Conclusions

Cardiac arrest is a notable complication in SCAD, mostly presenting with ventricular fibrillation. The prognosis of SCAD patients presenting with cardiac arrest did not differ from those without, reporting a similar rate of events both in-hospital and during long-term follow-up. STEMI presentation and angiographic type 2b were identified as independent predictors of cardiac arrest in SCAD.
Clinical characteristics and predictors of recurrence from the Australia-New Zealand Spontaneous Coronary Artery Dissection (ANZ-SCAD) registry
Authors: Dang Q , Psaltis P , Burgess S , Chandrasekhar J , Fairley S , Mukherjee S , Marathe J , Puri A , Zaman S
Published: October 2024

Background

Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of acute coronary syndrome (ACS), particularly in young women. Our understanding of SCAD remains incomplete with limited prospective data on determinants of SCAD recurrence.

Purpose

We aimed to describe the clinical characteristics, incidence and predictors of SCAD recurrence and major adverse cardiovascular events (MACE) in patients with SCAD from a large, multicentre registry.

Methods

Observational, multi-centre prospective and retrospective cohort study recruiting patients with SCAD from 23 hospitals in Australia and New Zealand. Patients aged=>18 years with SCAD and an ACS were eligible for inclusion. Prospectively recruited patients gave their informed consent while a waiver of consent was granted for retrospectively recruited patients. An independent core laboratory adjudicated invasive coronary angiography images to confirm the diagnosis of SCAD. The primary outcome was SCAD recurrence, defined as de novo spontaneous dissection with new ACS symptoms and cardiac enzyme elevation, not due to extension of the index lesion. Cox proportional hazard models were used to evaluate the association between SCAD recurrence and predefined clinical variables.

Results

From a total 487 patients recruited, 423 (132 prospective and 291 retrospective) patients with SCAD confirmed on core laboratory review were included for analysis. Mean age was 52.4±10.7 years, 89.7% were female and 73.1% were Caucasian. At discharge, 75.2% were on beta-blockers, 27.9% single antiplatelet and 61.9% dual antiplatelet (DAPT). At 15 (interquartile range 5-36) months median follow-up, SCAD recurrence occurred in 3.3%, with an overall MACE of 6.6%. On multivariate analysis, the presence of fibromuscular dysplasia (FMD) or other extra-cardiac vascular abnormalities [adjusted hazard ratio (HR) 5.63, 95% confidence interval (CI), 2.09-15.3, p<0.001], and past history of stroke (adjusted HR 7.99, 95% CI, 1.51-42.4, p=0.015) were associated with higher SCAD recurrence. Discharge beta-blockers was not independently associated with SCAD recurrence, while dual antiplatelet therapy that combined ticagrelor with aspirin was associated with a higher risk of recurrence (adjusted HR 2.47, 95% CI, 1.9-15.6, p=0.048).

Conclusion

SCAD recurrence comprised half of overall MACE in people with SCAD. The risk of SCAD recurrence was more than 5-fold higher in patients with FMD or other extra-cardiac vascular abnormalities. Dual-antiplatelet therapy that comprised ticagrelor and aspirin was associated with a higher risk of SCAD recurrence.
Artificial intelligence-based automated plaque quantification from CCTA to predict acute coronary syndrome on top of obstructive or ischemic coronary artery disease
Authors: Bar S , Maaniitty T , Nabeta T , Bax J J , Earls J P , Min J , Saraste A , Knuuti J
Published: October 2024

Background

Artificial intelligence (AI)-based quantitative computed tomography (AI-QCT) is a novel tool for automated plaque characterization and quantification from coronary computed tomography angiography (CCTA). The prognostic value of various AI-QCT plaque types on top of the presence of obstructive or ischemic coronary artery disease (CAD) is unknown.

Purpose

To investigate the added prognostic value for acute coronary syndrome (ACS) of AI-QCT total plaque burden (percent atheroma volume (PAV) %), and its subcomponents non-calcified plaque burden (NCPB), low-attenuation plaque burden (LAP), and calcified plaque burden (CPB) (%) on top of obstructive or ischemic CAD.

Methods

A cohort of 2007 symptomatic patients having undergone CCTA and selective downstream PET perfusion for suspected CAD was analyzed. Patients with prior or early elective revascularization within 6 months from CCTA were excluded. Obstructive CAD was defined as ≥1 vessel with >50% visual stenosis, and ischemic CAD as absolute hyperemic myocardial blood flow ≤2.3 ml/g/min in ≥2 adjacent segments on 15O-H2O PET. Multivariable Cox regressions adjusted for clinical confounders (age, sex hypertension, typical angina) including each plaque type separately (per 1.0%) on top of obstructive or ischemic CAD, respectively, were performed. The amount of LAP was <1% and therefore pooled together with NCPB.

Results

Throughout a median follow-up of 7 years, 72/2007 patients experienced ACS (50 myocardial infarction, 22 unstable angina). On top of obstructive CAD, all plaque types were independent predictors of ACS (Figure 1A), however according to the C-indexes (p-value vs. obstructive CAD), only PAV (C-index=0.814, p=0.010) and NCPB+LAP (C-index=0.818, p=0.014), but not CPB (C-index=0.800, p=0.066) significantly improved the prediction of ACS on top of obstructive CAD (C-index=0.790) (Figure 2A). On top of ischemic CAD (1967 patients, 66 events), all plaque types were also independent predictors of ACS (Figure 1B). But, similarly, according to the C-indexes (p-value vs. ischemic CAD), only PAV (C-index=0.818, p=0.003), and NCPB+LAP (C-index=0.818, p=0.005), but not CPB (C-index=0.798, p=0.054) significantly improved the prediction of ACS on top of ischemic CAD (C-index=0.776) (Figure 2B). NCPB+LAP alone performed similarly as PAV on top of obstructive (p=0.554) and ischemic CAD (p=0.991) (Figure 2).

Conclusions

Among patients with native coronary arteries treated medically, AI-based plaque quantification significantly improved the prediction of ACS on top of obstructive or ischemic CAD. The risk of ACS was largely related to NCPB+LAP, whereas CPB did not significantly improve risk stratification.Adjusted HR for ACS per plaque typeC-indexes for ACS
Prognostic influence of the neurological complications in patients supported with venoarterial extracorporeal membrane oxygenation
Authors: Alonso Fernandez De Gatta M , Hernandez Martos A V , Diego Nieto A , Gonzalez Cebrian M , Toranzo Nieto I , Barrio Rodriguez A , Gonzalez Calle D , Merchan Gomez S , Martin Herrero F , Sanchez P L
Published: October 2024

Background

Neurologic injuries including ischemic or hemorrhagic stroke and hypoxic-ischemic encephalopathy are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO).

Purpose

Our objective was to analyze the prognostic influence of neurological injuries on in-hospital survival.

Methods

Retrospective analysis of consecutive VA-ECMO cases in a referal center. We studied the neurological diagnoses and the results of complementary tests (brain computed tomography –CT- and electroencephalogram –EEG-) and their influence on in-hospital evolution.

Results

238 VA-ECMO were implanted between oct 2013-jan 2024. Baseline, admission and evolution characteristics are collected in the table.

58.4% of patients had suffered cardiac arrest (prior to VA-ECMO implantation, and extracorporeal cardiopulmonary resuscitation was performed in 28.6% of cases.

6 (2.5%) suffered intracranial hemorrhage, 13 (5.5%) ischemic stroke and 40 (16.8%) some degree of hypoxic-ischemic encephalopathy.

In-hospital survival was 32.4% (n=77). In 17.2% of the cases neurological damage influenced death (adequacy of therapeutic effort or non-escalation of therapies) and in 14.7% of cases death was directly due to neurological cause (table).

Survival was lower in patients with ischemic (stroke survival 23.1% vs no stroke 33.2%, p=0.555) or hemorrhagic stroke (16.7% vs 33%, p=0.667), although without statistically significant differences.

The presence of hypoxic brain damage was related to lower hospital survival (survival in patients with encephalopathy 15% vs. without 36.8%, p=0.009).

Best EEG pattern registered was related to survival: I survival 33.3% and II 12.5% (good prognosis), III 25% (uncertain prognosis), IV 16.7% and V 0% (poor prognosis), p=0.048. The presence of status epilepticus showed a non-statistically significant trend towards lower survival (survival status 0% vs no estatus 25%, p=0.082).

VA-ECMO preimplantation cardiac arrest was associated with the occurrence of encephalopathy (encephalopathy 84% vs. not 40%, p=0.049). The duration of cardiac arrest and lactate before VA-ECMO implantation were significantly higher as the EEG pattern was worse (figure).

Conclusions

Neurological damage is relevant in patients under VA-ECMO support, being a determining factor in death in up to 17.2% of patients. Hypoxic-ischemic encephalopathy was associated with lower survival, with the EEG pattern associated with previous cardiac arrest, its duration and lactate.Table.Baseline, admission and follow-upFigure.Cardiac arrest, lactate and EEG
Factors associated with 30-day mortality in patients receiving mechanical circulatory support for cardiogenic shock
Authors: Bogerd M , Peters E J , Ten Berg S , Griffioen A M , Timmermans M J C , Meuwissen M , Otterspoor L C , Engstrom A E , Vlaar A P J , Van Geuns R J M , Henriques J P S
Published: October 2024

Introduction

Mechanical circulatory support (MCS) is often deployed in patients with refractory cardiogenic shock complicating acute myocardial infarction (AMI-CS). Nevertheless, the mortality rate in these patients remains utterly high, around 50%.

Purpose

The aim of this study was to identify patient characteristics associated with 30-day mortality in patients receiving MCS for AMI-CS.

Methods

In the Netherlands, all patients undergoing percutaneous coronary intervention (PCI) are prospectively entered in the Netherlands Heart Registration (NHR). Additional data were retrieved for all CS patients between 2017-2021 in 14 Dutch hospitals, including MCS usage. Survivors and non-survivors amongst MCS treated patients were compared to identify patient characteristics associated with 30-day mortality. In addition, multivariate logistic regression analysis on imputed data was performed to quantify these associations in adjustment for confounders.

Results

MCS was deployed in 516 (23.3%) of all AMI-CS patients. MCS patients had a mean age of 64.2 (± 12.5) years and 74.6% were male. An intra-aortic balloon pump (IABP) was used in 49.0% of the patients. Impella, extracorporeal membrane oxygenation (ECMO) and multiple devices were used in 18.2%, 13.2% and 18.4% respectively. The overall 30-day mortality rate was 55.0%. At baseline, MCS survivors were younger (62.8 vs 65.2, p=0.03), had diabetes less often (18.4 vs. 28.0, p=0.02), and presented with a higher mean arterial pressure (MAP) (77.9 vs. 71.7, p<0.01). An out-of-hospital cardiac arrest (OHCA) preceded in 34.3% of the survivors versus 42.0% of the non-survivors (p=0.09). Survivors also had lower admission levels of lactate (5.0 vs. 7.8, p<0.01), glucose (12.1 vs. 15.2, p<0.01) and creatinine (94 vs. 115, p<0.01). Multivessel disease (MVD) was present less frequently in survivors compared to non-survivors (62.1% vs. 74.2%, p<0.01). In-hospital cardiac arrest (IHCA) occurred less often in survivors both prior to PCI (8.2% vs. 18.0%, p<0.01) and during PCI (22.8% vs. 34.6%, p<0.01). After multivariate logistic regression, higher age (OR 1.04, 95%CI: 1.02-1.05), resuscitation prior to (OR 2.11, 95 %CI: 1.09-4.09) or during PCI (OR 1.58, 95% CI: 1.01-2.47) and the presence of MVD (OR 2.07, 95% CI: 1.32-3.25) were independently associated with 30-day mortality in AMI-CS patients who received MCS.

Conclusion

In AMI-CS patients who received MCS, older age, the occurrence of an IHCA prior to or during PCI, and the presence of MVD were independently associated with an increased 30-day mortality.Figure 1.Table 1.
Does inflammation matter in cardiogenic shock?
Authors: Procopi N , Sulman D , Kerneis M , Rouanet S , Sbissa Y , Beaupre F , Devos P , Guedeney P , Barthelemy O , Chommeloux J , Hekimian G , Combes A , Silvain J , Montalescot G , Zeitouni M
Published: October 2024

Background

The current Society for Cardiovascular Angiography and Interventions (SCAI) shock stage classification does not include the systemic inflammatory response to risk stratify patients with cardiogenic shock.

Purpose

To evaluate the prognostic impact of the inflammatory response, on top of the SCAI shock classification, during cardiogenic shock using C-Reactive protein (CRP).

Methods

We analyzed CRP levels and SCAI shock classification in consecutive patients admitted for cardiogenic shock between January 2010 and December 2020, included in the ACTION-SHOCK registry of our tertiary center. Patients with ongoing sepsis or other extracardiac causes for elevated CRP were excluded. Using logistic regression method, we assessed both the association between CRP levels at admission and all-cause mortality at 90 days, and the value of the addition of baseline CRP level to SCAI stage of shock for the prediction of 90-day mortality.

Results

Among 755 patients admitted with cardiogenic shock (median age 61 years, interquartile range [IQR] 50-72, 27% of female), only 128 (17%) had normal values of CRP (< 5mg/L) at admission. Median CRP at admission was 19mg/l (IQR 6-55). There was an association between 90-day mortality and baseline CRP (Odds Ratio [OR] = 1.02, 95% Confidence Interval [95%CI] 1.01-1.03 per 5mg/L of CRP, p=0.004), still significant after adjustment on clinical and biological variables associated with 90-day mortality in univariate analysis, including the SCAI shock stage (adjusted OR 1.02, 95%CI 1.01 - 1.03 per 5 mg/L, p=0.042). The addition of CRP increased the accuracy of the SCAI shock stages for the prediction of 90-day mortality (Area under the Curve increased from 0.59, 95% CI 0.50 - 0.66 to 0.65, 95% CI 0.61 - 0.72). Interestingly, the association of CRP with mortality was driven by patients in SCAI shock classes A and B (figure).

Conclusions

CRP elevation was frequently observed in this population of patients with any cause of cardiogenic shock and was associated with 90-day mortality. This was particularly evident for patients in lower SCAI shock stages on admission.Figure 1
Aortic valve disease augments vesicular microRNA-145-5p to regulate the calcification of valvular interstitial cells via cellular crosstalk
Authors: Hosen D R , Goody M E D , Christmann M E D , Nehl M R S , Wilhelm-Juengling D R , Abplanalp D R , Moore Iv D R , Uchida M R , Zimmer D R , Bakhtiary D R , Pfeifer D R , Latz D R , Jansen M E D , Nickenig D R
Published: October 2024

Rationale: Aortic valve stenosis (AVS) is a major contributor to cardiovascular death in the elderly population worldwide. MicroRNAs (miRNAs) are highly dysregulated in patients with AVS undergoing surgical aortic valve replacement (SAVR). However, miRNA-dependent mechanisms regulating inflammation and calcification or miRNA-mediated cell-cell crossstalk during the pathogenesis of AVS are still poorly understood. Here, we explored the role of extracellular vesicles (EV)-associated miR-145-5p, which we showed to be highly upregulated upon valvular calcification in AVS in mice and humans.

Methods

Human TaqMan miRNA arrays identified dysregulated miRNAs in aortic valve tissue explants from AVS patients compared to non-calcified valvular tissue explants of patients undergoing SAVR. Echocardiographic parameters were measured in association with the quantification of dysregulated miRNAs in a murine AVS model. In vitro calcification experiments were performed to explore the effects of EV-miR-145-5p on calcification and crosstalk in valvular cells. To dissect molecular miRNA signatures and their effect on signaling pathways, integrated OMICS analyses were performed. RNA sequencing (RNA-seq), high-throughput transcription factor (TF) and proteome arrays showed that a number of genes, miRNAs, TFs, and proteins are crucial for calcification and apoptosis, which are involved in the pathogenesis of AVS.

Results

Among several miRNAs dysregulated in valve explants of AVS patients, miR-145-5p was the most highly gender-independently dysregulated miRNA (AUC, 0.780, p-value, 0.01). MiRNA arrays utilizing patient-derived- and murine aortic-stenosis samples demonstrated that the expression of miR-145-5p is significantly upregulated and correlates positively with cardiac function based on echocardiography. In vitro experiments confirmed that miR-145-5p is encapsulated into EVs and shuttled into valvular interstitial cells. Based on the integrated OMICs results, miR-145-5p interrelates with markers of inflammation, calcification, and apoptosis. In vitro calcification experiments demonstrated that miR-145-5p regulates the ALPL gene, a hallmark of calcification in vascular and valvular cells. EV-mediated shuttling of miR-145-5p suppressed the expression of ZEB2, a negative regulator of the ALPL gene, by binding to its 3' untranslated region to inhibit its translation, thereby diminishing the calcification of target valvular interstitial cells.

Conclusion

Elevated levels of pro-calcific and pro-apoptotic EV-associated miR-145-5p contribute to the progression of AVS via the ZEB2-ALPL axis, which could potentially be therapeutically targeted to minimize the burden of AVS.
Left ventricular mass index and prognosis of symptomatic severe aortic stenosis in women and men
Authors: Avakian S D , Tarasoutchi F , Mansur A
Published: October 2024

Background

Symptomatic severe aortic stenosis (AS) requires surgical (SAVR) or transcatheter aortic valve replacement (TAVR), and many patients are on the procedure waiting list. The diagnosis of severe AS is based on clinical and echocardiographic criteria, such as left ventricular ejection fraction (LVEF), aortic valve area (AVA), mean transvalvular gradient, and peak aortic jet velocity. However, there is a gap in knowledge regarding the influence of left ventricular mass on the prognosis of these patients, especially considering differences between women and men.

Purpose

To evaluate the influence of left ventricular mass index (LVMi) on the mortality of women and men with severe AS awaiting SAVR or TAVR.

Methods

A prospective study analysed the death rate in 531 outpatients with symptomatic severe AS with mean transvalvular gradient ≥40 mmHg, AVA ≤1.0 cm2, or peak aortic jet velocity ≥4.0m/s at echocardiography with the indication for TAVR or SAVR in the period from April 2020 to February 2024. Baseline data included analysis of clinical characteristics, echocardiographic variables, and the presence of coronary artery disease (CAD). Statistical analyses were performed using the Kaplan-Meier (K-M) and Cox proportional hazards methods to analyze mortality rates in women and men.

Results

The mean age was 74.7±11.6 years, with 283 (53.3%) men. Over a follow-up period of 2.67±1.22 years, death occurred in 165 (31.1%), 148 (86%) due to cardiovascular disease, and 152 (92%) had heart failure (HF) NYHA II to IV, 51 (9,6%) had angina, and syncope in 11 (2.1%) of the patients. Patients who died had lower LVEF (61.4%±8.9% vs. 58.8%±10.8%; p=0.008) and higher LVMi (125.3±32.5 g/m2 vs. 115.5±29.3 g/m2; p=0.001). Angina, syncope, hypertension, dyslipidemia, diabetes, smoking, atrial fibrillation, and CAD prevalence were similar in living patients and in those who died. Both groups had similar echocardiographic data, such as left atrial volume, mean transvalvular gradient, and peak jet velocity. TAVR and SAVR were done in 111 (20.9%) and 162 (30.5%) patients. Of these, 21 (18.9%) and 20 (12.4%) died during follow-up, respectively. Cumulative mortality of all patients was higher with LVMi >115 g/m2 compared to ≤115 g/m2 (p=0.008)(Figure). In women but not in men, cumulative mortality was higher with LVMi >115 g/m2 compared to ≤115 g/m2 (p=0.046). Cox multivariate analysis, adjusted for LVEF, LVMi, CAD, and age, showed LVMi as an independent variable for death [HR=1.50 (95%CI: 1.10-2.05); p=0.011]. LVEF [HR=0.97 (95%CI: 0.95-0.99); p=0.009] and LVMi [HR=1.75 (95%CI: 1.10-2.79); p=0.016] were independent variables for death in women, but not in men.

Conclusion

Women with higher LVMi and lower LVEF should have valve intervention prioritized.Figure
Lead-related tricuspid regurgitation: an important phenotype seen through the lens of computed tomography
Authors: Margonato D , Enriquez-Sarano M , Hamid N , Wang C , Fukui M , Phichaphop A , Okada A , Sorajja P , Bapat V , Cavalcante J
Published: October 2024

Background

The imaging diagnostic approach of patients with cardiac implantable electronic devices (CIED)-related tricuspid regurgitation (TR) is undefined. Functional cardiac computed tomography angiography (4D-CTA) provides a complementary role to echocardiography in the evaluation of tricuspid valve (TV) apparatus and right ventricle (RV) remodeling, but the capability to assess lead-leaflet interaction is unknown.

Purpose

To evaluate the role of 4D-CTA anatomical and morphological diagnostic assessment in a cohort of patients with severe TR and CIED vs those without.

Methods

Clinical, echocardiographic and CTA data were collected from two quaternary centers for patients with severe TR and a CIED evaluated between January 2017 to October 2023. Functional and morphological CTA information assessed lead-leaflet relationship to divide patients in those with lead-related TR, those with no lead-TR causal relationship, and those with severe isolated TR but without CIED. Primary end-point was the occurrence of all-cause death.

Results

A total of 143 patients were identified, roughly dividng the cohort into thirds. Baseline characteristics and imaging characteristics of these 3 groups revealed important differences suggesting a more advanced patophysiology phenotype for those with lead-related TR, particularly presenting both the largest 4D-CTA-derived TV maximum coaptation gap and anatomical regurgitant orifice area (see Figure 1).

At regression analysis, time from CIED implantation (OR 1.01, CI 1.00-1.09, p=0.031) and >3 leaflets valve morphology (OR 2.90, CI 1.01-8.32, p=0.040) were independently associated with lead-related TR.

After a median follow-up of 18 months, the primary end-point occurred in 36 patients (25%) and was more common among patients with lead-related TR (p-value overall= 0.007, see Figure 2). While no differences in the rate of TV intervention were found, excessive mortality persisted for lead-related TR group even after adjustement for age and gender (HR 6.49, CI 1.72-14.47, p=0.006).

Conclusion

Systematic 4D-CTA in patients with severe TR and presence of a CIED, identified a large number of patients with lead-related TR with important functional and anatomical implications including greater TR severity and > 3 leaflets. These findings appear to have prognostic relevance that might have decision-making implications for patient management.Figure 1Figure 2
Causal association of serum calcium, phosphate, vitamin D, parathyroid hormone, and FGF23 with the risk of aortic stenosis
Authors: Nie W , Zhao Q , Liu J
Published: October 2024

Aim

Disorders of mineral metabolism, including elevated levels of serum calcium, phosphate, 25-hydroxyvitamin D (25OH-VitD), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), have been reported in patients with calcific aortic valve stenosis (CAVS). However, evidence of the causal role of mineral metabolism in CAVS is still lacking. We aimed to investigate the causality between mineral metabolism and CAVS.

Methods

A systematic pipeline combining Mendelian randomization (MR), Steiger directionality test, colocalization analysis, protein-protein network, and enrichment analysis was applied to investigate the causal effect. Genome-wide association study (GWAS) and protein quantitative trait loci data for mineral metabolism markers were extracted from large-scale meta-analyses. Summary statistics for CAVS were obtained from two independent GWAS datasets as discovery and replication cohorts (n=374,277 and 653,867).

Results

In MR analysis, genetic mimicry of serum FGF23 elevation was associated with increased CAVS risk [ORdiscovery=3.081 (1.649-5.760), Pdiscovery=4.21×10-4; ORreplication=2.280 (1.461-3.558), Preplication=2.82×10-4] without evidence of reverse causation (Psteiger=7.21×10-98). Strong colocalisation association with CAVS was observed for FGF23 expression in the blood (PP.H4 = 0.96). Additionally, we identified some protein-protein interactions between FGF23 and known CAVS causative genes. Serum calcium, phosphate, 25OH-VitD, and PTH failed to show causal effects on CAVS at Bonferroni-corrected significance (all P>0.05/5=0.01).

Conclusions

Elevated serum FGF23 level is a causal risk factor for CAVS, and its mechanism of action in CAVS development may be independent of its function in regulating mineral metabolism. Hence, FGF23 may serve as a circulating marker and a promising preventive target for CAVS, warranting further investigation.
Electrocardiographic criteria for the diagnosis of left ventricular hypertrophy in patients with severe aortic stenosis
Authors: Emer Egypto Rosa V , Pires L J N T , Nazzetta D C , Tessari F C , Campos C M , Lopes M P , Andrade C E , Trentin B R P , Fernandes J R C , Sampaio R O , Tarasoutchi F
Published: October 2024

Introduction

There is a lack of data regarding the performance of current electrocardiographic (EKG) criteria for left ventricular hypertrophy (LVH) in patients with severe aortic stenosis (AS).

Purpose

To test the performance of the current EKG scores to diagnosis LVH in AS patients, and also to compare the performance of a new proposed score.

Methods

The present study evaluated 80 patients with severe AS that underwent cardiac magnetic resonance to diagnose LVH, defined as left ventricular indexed mass of 95 g/m² for female and 115 g/m² for male patients. The EKG criteria used for left ventricular hypertrophy were Sokolow-Lyon criteria, Romhilt-Estes point score system, Cornell voltage criteria and Peguero-Lo Presti criteria.

Results

Among the 80 patients included in analysis, 58.7% were male and the mean age was 64±8 years. There was a high prevalence of comorbidities, highlighting diabetes (32.5%), hypertension (67.5%), atrial fibrillation (5.0%) and coronary artery disease (11.3%). Regarding echocardiogram, the median left ventricle ejection fraction was 64 (56-68)% and the median indexed aortic valve area was 0.43 (0.35-0.49) cm²/m². Cardiac magnetic resonance analysis demonstrated a mean left ventricle mass of 168±55g, and the LVH incidence was 26.3%. Regarding EKG, Strain pattern was found in 49.1% of the patients, Cornell voltage criteria was positive in 51.3%, Sokolow-Lyon criteria in 51.3%, Romhilt-Estes point score system in 42.5% and Peguero-Lo Presti criteria in 61.3%. Discriminative capacity of electrocardiographic criteria for LVH is shown in Figure 1. Peguero-Lo Presti score had the best diagnostic accuracy in the overall population and in male sex (AUC 0.776), while Cornell voltage criteria had the best diagnostic accuracy in female patients (AUC 0.776). Based on linear regression model, the proposed score was created to predict LVH at cardiac magnetic resonance: 48 + (1.3 x Deepest S wave) + (0.5 x S wave in V1 or V2 plus R wave in V5). The proposed score cutoff value of 90.5 mm had a sensitivity of 0.765 and specificity of 0.707 (for male sex: 0.769 and 0.655, respectively; for female sex: 0.750 and 0.759, respectively). Compared to the scores described in the literature, the proposed score had the best area AUC for the overall population (Figure 1), for female and male patients (AUC 0.796, 0.819 and 0.780, respectively).

Conclusion

In patients with severe AS, the proposed score had the best diagnostic accuracy compared to the scores described in the literature for LVH identification, followed by Peguero-Lo Presti score, even when analyzed based on gender. Besides, the proposed score had also acceptable sensitivity and specificity for LVH detection.AUC of electrocardiographic scores.
Prognostic impact of left ventricular myocardial work in patients undergoing surgery for primary mitral regurgitation
Authors: Nabeta T , Peters F , Wu H , Palmen M , Tomsic A , Marsan N A , Bax J J , Van Der Bijl P
Published: October 2024

Background

Although left ventricular ejection fraction (LVEF) is widely used as a parameter for the assessment of LV systolic function, LVEF can overestimate LV systolic function in patients with severe mitral regurgitation (MR) due to its high load-dependency. Echocardiography-based, left ventricular myocardial work (LVMW) can assess LV function by incorporating LV afterload.

Purpose

This study aims to evaluate the prognostic value of LVMW indices in patients with primary MR undergoing mitral valve surgery.

Methods

Individuals who underwent mitral valve surgery for severe primary MR were included. All patients underwent transthoracic echocardiography before surgery. LVMW was derived from a vendor-specific package which integrates LV global longitudinal strain with sphygmomanometric blood pressure to construct pressure-strain loops during the cardiac cycle. (Figure 1) For the LVMW indices, previously-established normal values were used as thresholds. The primary endpoint was all-cause mortality after mitral valve surgery.

Results

A total of 309 patients (mean age 63 ± 12 years, 68% male) with severe, primary MR who underwent surgery, were included. The mean LV global work index (LVGWI) was 1977 ± 537 mmHg% and 132 (43%) patients had impaired LVGWI (≤ 1900 mmHg%). During a median follow-up of 5.0 years (interquartile range, 2.5-8.9), 27 (8.7%) patients died after mitral valve surgery. Patients with impaired LVGWI or LV GLS (≤ 20%) had lower survival rates compared to the group with preserved LVGWI (p <0.01) or LVGLS (p = 0.02), whereas there was no significant difference in the survival rate between patients with LVEF ≤ 60% and > 60%. (Figure 2) Furthermore, LVGWI ≤ 1900 mmHg% demonstrated incremental prognostic value over LVGLS (p = 0.049) for all-cause mortality.

Conclusions

In patients with severe, primary MR who underwent surgery, impaired pre-operative LVGWI was associated with a higher mortality risk. In addition, impaired LVGWI had incremental prognostic value over LVGLS. Based on these findings, LVMW is a promising parameter for predicting postoperative outcome and determining the optimal timing of valve surgery in patients with severe, primary MR.Fig1.Echo-derived Myocardial workFig2.Kaplan-Meier curves
Epidemiological profile and mortality of infective endocarditis over the past decade: a systematic review and meta-analysis of 133 studies comprising 132,355 cases
Authors: Sagris M , Tzoumas A T , Xenos D X , Ntoumaziou A N , Kakargias F K , Liaquat W L , Patel R P , Nagraj S N , Kokkinidis D K , Tsioufis K T , Tousoulis D T , Palaiodimos L P
Published: October 2024

Background

Understanding the epidemiology of infective endocarditis (IE) is crucial in the context of an aging population, increased comorbidities, and the heightened occurrence of healthcare-associated cases. Comprehensive data on causative agents, affected valves, and associated mortality are essential for current clinical practice.

Methods

This systematic review was conducted according to the PRISMA guidelines. A random effects model meta-analysis was conducted. Eligible studies reporting outcomes on IE were identified through a search of the PubMed/Medline database from 2010 to 2021.

Results

One hundred-thirty-three studies with 132,584 patients from six continents were included in the analysis. The most common causative agents of IE were Staphylococci species in 36% of cases, followed by Streptococci species in 26% of cases and Enterococci species in 10% of cases. Of the studies providing further speciation, the predominant species was Staphylococcus aureus with an incidence of 29%, followed by Viridans Streptococcus with an incidence of 12%. We found an in-hospital/30-day mortality of 17% (CI: 16%-19%) from 109 studies worldwide. In the subgroup analysis, the highest mortality rates were observed in Latin America 33% (CI: 28%-38%) and Africa 25% (CI: 21%-30%), while the lowest mortality rates were reported in Oceania 13% (CI: 8%-19%), followed by North America 14% (CI: 11%-18%), Asia 15% (CI: 12%-18%), and Europe 17% (CI: 16%-19%). The aortic valve was affected in 46% of cases, followed by the mitral valve in 43%. Tricuspid valve IE and multivalvular IE were identified in 7% and 14% of the cases, respectively.

Conclusion

Our study highlights the shift in epidemiological profile of IE over the last decade with S. aureus identified as the most common causative microorganism of IE in almost one third of cases. IE remains a highly morbid and fatal condition with high mortality rates even in tertiary and high-expertise centers worldwide. While left-sided IE is by far more common, right-sided IE and multivalvular IE are not rare entities and should be considered early in the differential of patients presenting with suspected IE to decrease the risk of future complications.Global burden of infective endocarditis.
Clinical features of infective endocarditis affecting cardiac implantable electronic devices
Authors: Roldan Guerra A , Barreiro Mesa L , Aguayo Cano N , Urbano Sanchez C , Gonzalez Manzanares R , Crespin Crespin M , Lopez Aguilera J , Delgado Ortega M , Ruiz Ortiz M , Rodriguez Almodovar A , Esteban Martinez F , Mesa Rubio D , Pan Alvarez-Ossorio M
Published: October 2024

Introduction

Infective endocarditis (IE) is a serious condition with high rates of serious complications and mortality. Furthermore, implantation of cardiac electronic devices (peacemakers, ICD, CRT) has been increasing in recent years, with technique-associated infections being one of the main adverse events. Our goal was to analise clinical features of IE as associated with cardiac implantable electronic devices (IE-CIED) and its prognostic impact.

Methods

Prospective study of a cohort of patients diagnosed with IE in our centre from 1987 to 2022. A comparative analysis was performed between patients with IE not associated with cardiac implantable electronic devices (group 1) and those who did (group 2). Clinical, microbiological, echocardiographic and therapeutic variables were analysed and the prognostic impact was evaluated in terms of mortality.

Results

569 patients were analysed, of which 540 (94,9%) belonged to group 1, while 29 (5,1%) belonged to group 2. The mean age was higher in group 2 (65,1 years ±12,9 vs 55,7 years ± 18,7; p=0,011) with male predominance in both populations (67.5% overall). Patients with IE-CIED had a higher proportion of staphylococcus aureus (48.3% vs 19.7%; p<0.001) and staphylococcus epidermidis (34.5% vs 15.6%; p<0.001) infections; nosohusial endocarditis (56.5% vs 20.9%; p<0.001); and underlying heart disease (89.7% vs 67.3%; p=0.012). Furthermore, these patients had a higher proportion of tricuspid valve involvement (18.2% vs 81.8%; p<0.001). Regarding the approach, a higher percentage of surgery was performed in patients with IE-CIED (75.9% vs52.7%; p=0.015). On the other hand, patients with IE not associated to cardiac implantable electronic devices had a higher prevalence of cardiac complications (51.5%vs25.7%;p=0.003), defined as valvular rupture or perforation, pseudoaneurysm, abscess or intracardiac fistula; and central nervous system complications (17.2%vs2.9%;p=0.29).

No significative differences were found in terms of echocardiographic findings compatibles with IE, nor were there any differences in severe complications or early, late or total mort ality.

Conclusions

Infective endocarditis affecting cardiac implantable electronic devices is associated to higher prevalence of staphylococci, underlying heart disease and less involvement of the left heart chambers. Surgery was used to a greater extent in this patients. This entity does not imply a worse prognosis in terms of severe complications or mortality.Table 1.Proportion of IE-CIEDTable 2.Microbiology, mortality
Whole-exome sequencing to identify causative variants in cases of sudden cardiac death below 50 years
Authors: Aimo A , Modena M , Botto N , Vittorini S , Aretini P , Bonuccelli D , Emdin M , Di Paolo M , Giannoni A
Published: October 2024

Background

Sudden cardiac death (SCD) in individuals under 50 frequently remains unexplained, especially when no structural cardiac abnormalities are present, a condition known as sudden arrhythmic death (SAD). This study assesses the utility of whole exome sequencing (WES) with a comprehensive gene panel in elucidating the genetic foundations of SCD.

Methods

SCD autopsy cases from a university hospital (1995-2023) were analysed both retrospectively and prospectively. WES was conducted on 32 cases, employing a virtual panel of 1,304 genes. Variant prioritization was based on pathogenicity according to American College of Medical Genetics and Genomics guidelines.

Results

WES unveiled causative variants in 22 out of 32 cases (68% diagnostic yield). Of these, 12 cases (38%) possessed pathogenic or likely pathogenic variants, and 17 highly suspicious variants of uncertain significance (VUS/LP) were identified in 10 patients (31%). The diagnostic yield of our comprehensive panel (69%) surpassed that of major susceptibility gene panels, with 22% for primary susceptibility genes and 56% for the TruSight Cardio Panel. Half of the cases had multiple variants, underscoring the genetic complexity of SCD. Of the genes analysed, 18 were associated with cardiac disease on OMIM or ClinGen, while 9, unique to our panel, were linked to cardiac function but had disputed or limited disease associations.

Conclusions

WES with a specific gene panel, a scheme for variant prioritization, and a comprehensive, multidisciplinary approach to variant interpretation is an effective approach to genetic testing in SCD cases ≤50 years.Added value of WES
Usefulness of scintigraphy with [99mTc]Tc-DPD for the detection of transthyretin cardiac amyloidosis. Reference centre experience in an endemic area
Authors: Orta Tomas N , Soledad Salomon C , Ripoll Vera T , Rubi Sureda S , Fortuny Frau E , Bosch Rovira M T , Losada Lopez I , Gonzalez Moreno J , Cisneros Barroso E
Published: October 2024

Background

Cardiac amyloidosis (CA) is an infiltrative disorder caused by protein deposition, being transthyretin amyloidosis (ATTR) and primary amyloidosis (AL) the most common forms of CA. ATTR can occur in a hereditary form (ATTRv) or wild-type (ATTRwt). Our area is endemic for ATTRv due to the Val30Met mutation.

Purpose

To analyse the usefulness of scintigraphy with [99mTc]Tc-DPD (DPD-CS) in an endemic area and its relationship with the diagnostic of CA.

Methods

We conduct a retrospective study (04/2013-12/2022) of DPD-CS performed for suspected/screening of CA. Our acquisition protocol consists of performing planar images after 3h p.i.(anterior, left anterior oblique and left lateral) +/- SPECT/CT. The assessment of myocardial uptake was evaluated using the Perugini scale (PS: 0-3), considering 2 and 3 as positive scans. DPD-CS results were classified based on the suspicion of CA, according to the 2021 ESC guidelines (we considered cardiomyopathy if: left ventricle hypertrophy ≥12 mm + ≥3 typical signs/symptoms), as well as according to their final diagnosis: ATTRv, asymptomatic carriers, ATTRwt, AL, AA and other non-amyloid (NA) causes. Clinical findings were correlated with the results of the DPD-CS.

Results

509 DPD-CS were performed in 478 patients (median age:73 years [22-95], 62% men). Median follow-up: 4.17 years. 127/478 patients were classified with cardiomyopathy (131/509 DPD-CS) and 351/478 without cardiomyopathy (378/509 DPD-CS).

115/509 positive DPD-CS (PS-2: 17, PS-3: 98): 113 had cardiomyopathy (55 ATTRv, 60 ATTRwt) and 2 without cardiomyopathy (1 ATTRv, 1 asymptomatic carrier). These latter two patients developed cardiomyopathy during the follow-up.

394/509 negative DPD-CS (PS 0: 387, PS 1: 7): 18 with cardiomyopathy (1 ATTRv, 1 carrier, 3 AL and 13 NA) and 376 without cardiomyopathy (30 asymptomatic carriers, 88 ATTRv, 2 AA, 9 AL and 247 NA). One patient with cardiomyopathy and ATTRv had initial negative DPD-CS, but became positive DPD-CS on follow-up. All ATTRv without cardiomyopathy presented polyneuropathy.

Final diagnoses (according to DPD-CS number): 143 ATTRv (140 Val30Met, 2 Val122Ile, 1 Glu495Gln), 32 carriers (29 Val30Met, 2 Val122Ile, 1 His51Asn), 61 ATTRwt,12 AL, 2 AA and 259 NA. The analysis obtained after correlating the results of the DPD-CS regarding the presence of cardiomyopathy was: sensitivity 86.25%, specificity 99.47%, PPV 98.26% and NPV 95.43%.

Conclusion

Our study reaffirms the usefulness of DPD-CS in the non-invasive diagnosis of transthyretin CA. DPD-CS has an additional value in endemic areas for the early detection of CA in asymptomatic patients.
Protosappanin a protects DOX-induced myocardial injury and cardiac dysfunction by targeting ACSL4/FTH1 axis-dependent ferroptosis
Authors: Cui J , Chen Y , Yang Q , Zhao P , Yang M , Wang X , Mang G , Yan X , Wang D , Tong Z , Wang P , Wang N , Liu M , Zhang M , Yu B
Published: October 2024

Background

Doxorubicin (DOX) is a breakthrough drug in cancer therapy that mediates irreversible dosedependent cardiotoxicity with poor outcomes.Cardiomyocyte ferroptosis plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC). Agents that block DOX-induced cardiomyocyte ferroptosis may have clinical utility in the treatment of DIC.

Purpose

We pursued the potential role of protosappanin A (PrA), an active constituent extract from traditional Chinese hematoxylin, on DOX-induced cardiac dysfunction.

Methods

We established acute DIC murine models to investigate the role of PrA in DOX-induced cardiotoxicity.In vivo, western blotting was performed to assess the levels of classical proteins associated with the iron death pathway, while Prussian blue staining and DHE staining were utilized to measure iron ion levels and reactive oxygen species respectively. In vitro, DOX-induced H9C2 cells model was established and the level of ferroptosis-related indicators were detected,such as iron, reactive oxygen species (ROS), and lipid peroxides. Proteome microarray, Molecular docking and Cellular thermal shift assay were used to identify the molecular targets (ACSL4 and FTH1) of PrA. Pull-down assay was used to validate the interaction of PrA with ACSL4 and FTH1 proteins in lysates from H9c2 cells, and explored theirs possible mechanism of action. Finally, we investigated the in vivo effect of PrA treatment in mice challenged with a myocardial ischemia-reperfusion mouse model.

Results

We report for the first time that PrA ameliorates myocardial damage and cardiac dysfunction in a mouse model of DIC. PrA improves DOX-induced ferroptotic phenotypes in cardiomyocytes, as demonstrated by reduced production of iron, reactive oxygen species (ROS), and lipid peroxides, thereby preserving mitochondrial homeostasis. PrA physically combines with the ferroptosis-related protein acyl-CoA synthetase long-chain family member 4 (ACSL4) and ferritin heavy chain 1 (FTH1), thus conferring the following regulatory mechanisms: PrA inhibits ACSL4 phosphorylation and subsequent phospholipid peroxidation; PrA prevents FTH1 autophagic degradation and subsequent ferrous ions (Fe2+) release. Notably, the cardioprotective and antiferroptotic activities of PrA are verified in a myocardial ischemiareperfusion mouse model.

Conclusion

Our studies indicate for the first time that PrA has a superior protective effect against DOX-induced cardiotoxicity via inhibiting a dual ferroptosis-assistance mechanism of the ACSL4/FTH1-dependent axis. We unveil a novel pharmacological inhibitor that targets ferroptosis, highlighting additional therapeutic options for chemodrug-induced cardiotoxicity and ferroptosis-triggered disorders.
Incidence and risk factors for development of left ventricular hypertrophy in Fabry disease
Authors: Monda E , Bakalakos A , Lachmann R , Syrris P , Limongelli G , Murphy E , Hughes D , Elliott P M
Published: October 2024

Background

Left ventricular hypertrophy (LVH) is the principal cardiac manifestation of Fabry disease (FD). This study aimed to determine the incidence and predictors of LVH development in a contemporary cohort of patients with FD and no LVH at baseline evaluation.

Methods

Consecutively referred adult (age ≥16 years) patients with FD were enrolled into an observational cohort study. Patients were prospectively followed in a specialist cardiomyopathy centre and the primary endpoint was the first detection of LVH (left ventricular mass index (LVMi) ≥115 g/m2 in men and ≥95 g/m2 in women).

Results

From a cohort of 393 patients, 214 (age 35.8 ±13.8 years; 61 [29%] males) had no LVH at first evaluation. During a median follow-up of 9.4 years (interquartile range [IQR] 4.7-12.7), 55 patients (24.6%) developed LVH. The estimated incidence of LVH was 11.3% (95% confidence interval [CI] 6.5-16.1) at 5 years, 29.1% (95%CI 21.5-36.7) at 10 years, and 45.0% (95%CI 33.8-62.4) at 15 years of follow-up. On multivariable analysis, independent predictors for LVH development were age (hazard ratio [HR] 1.04 [95%CI 1.02-1.06] per 1 year increase, p-value <0.001), male sex (HR 2.90 [95%CI 1.66-5.09], p-value <0.001), and an abnormal ECG (HR 3.10 [95%CI 1.72-5.57], p-value <0.001). The annual rate of change in LVMi was +2.77 (IQR 1.45-4.62) g/m2/year in males and +1.38 (IQR 0.09-2.85) g/m2/year in females (p-value <0.001).

Conclusions

Approximately one quarter of FD patients developed LVH during follow-up. Age, male sex, and ECG abnormalities were associated with a higher risk of developing LVH in patients with FD.Central Illustration