bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of discontinuing proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors on clinical outcomes
Authors: Tsubata H , Wakana N , Yanishi K , Nakanishi N , Zen K , Nakamura T , Matoba S 
Published: October 2024

Abstract

Background/Introduction
Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have demonstrated efficacy in lowering low-density lipoprotein cholesterol (LDL-C) levels and reducing the risk of cardiovascular events. Despite these advantages, some patients are unable to continue the use of PCSK9 inhibitors due to financial or other reasons. Limited clinical studies have been conducted to investigate the clinical outcomes of patients discontinuing PCSK9 inhibitors for various reasons.

Purpose
This study aims to specifically investigate patients who were unable to continue PCSK9 inhibitors, with a particular focus on those discontinuing due to financial or other reasons. The primary objective is to assess the impact of discontinuation on major adverse cardiovascular events (MACE).

Methods
This study focused on 205 Japanese patients who received PCSK9 inhibitors between July 2016 and December 2023. The clinical outcomes of patients who continued or discontinued PCSK9 inhibitors were comprehensively compared. The primary endpoint was major adverse cardiovascular events (MACE), encompassing cardiovascular death, coronary revascularization, target lesion revascularization (TLR), and fatal or non-fatal myocardial infarction (MI).

Results
Among 205 patients (median age: 69 years; interquartile range [IQR]: 60-76 years 68% male), the median follow-up was 413 days (IQR, 49-1148 days). At one year, the median LDL-C was 43mg/dL, and 158 patients (77%) achieved LDL-C &lt;70 mg/dL. During the follow-up, 64% (131 patients) continued PCSK9 inhibitors, while 36% (74 patients) discontinued. Of the discontinuation group, 30% (22 patients) cited financial problems, 24% (18 patients) clinical stability, and 12% (9 patients) patient preference. Multivariate Cox regression analysis revealed that the group discontinuing PCSK9 inhibitors had a higher incidence of MACE than the group that continued (hazard ratio: 1.84; 95% confidence interval: 1.02 to 3.55; p=0.05).

Conclusions
This study suggests an increased risk of MACE when PCSK9 inhibitors are discontinued for financial or other reasons. This insight is vital for healthcare management and decision-making among medical practitioners.PCSK9: continuation vs discontinuation
Obesity and its impact on functional capacity: understanding the interplay for health management
Authors: Nedeljkovic I , Nedeljkovic Arsenovic O , Ostojic M M , Djordjevic Dikic A , Giga V , Banovic M , Boskovic N , Dedic S , Polovina S , Micic D , Beleslin B 
Published: October 2024

Abstract

Background
Cardiopulmonary exercise testing (CPET) plays a significant role in evaluating obese individuals due to the unique physiological challenges they face during exercise. As diastolic function is impaired in majority of morbidly obese pts, combination of CPET with diastolic stress echocardiography may add more information to objective assessment

Objective
To assess the value of combined stress echo CPET (ESE-CPET) in assessment of diastolic function in morbidly obese pts.

Methods
We studied 400 pts (74% female, age 39.2±9.9 years) referred for bariatric surgery. Echocardiographic measurements have been performed before CPET and immediately after the test. CPET was performed on treadmill (maximal Bruce) with breath-by-breath gas analysis. We measured both peak oxygen consumption (peakVO2) and VO2 at anaerobic threshold (AT), as well as other ventilatory and hemodynamic parameters.

Results
Mean BMI was 44± kg/m2. Left ventricular ejection fraction was 63.5±5.6%. Mean VO2 at AT was 17±2 ml/kg/min, mean Peak VO2 was 19±4 ml/kg/min. Resting eho : mitral E to A wave (E/A),deceleration time ( Dt) and mitral E to mitral anular E’ (E/E’) values did not correlate significantly with parameters of CPET. However, there was significant correlation between maximal E/ E’ with PeakVO2 and VO2 at AT (p&lt;0.001), , Pet CO2 (p=0.0001) as well as with myocardial performance index as a parameter of global left ventricular function (p&lt;0.001) However, VE/VCO2 was the strongest predictor of increase in E/ E’≥ 15 indicating the importance of ventilatory parameters and dynamic tests.

Conclusions
Assessment of diastolic function in morbid obese patients represents a great challenge to cardiologists because obesity contributed significantly to deterioration of diastolic function. Combined stress echo CPET showed the advantage and benefit of integrated evaluation of both pulmonary and cardiovascular function representing as a significant step forward in assessment of diastolic function overcoming the limitations of resting echocardiography and CPET performed as a single test.
Rosuvastatin effect on atherosclerotic plaque microcalcification
Authors: Santos M , Rosa J , Silva R , Castelo Branco M , Abrunhosa A , Grine M , Gomes A , Goncalves L , Ferreira M 
Published: October 2024

Abstract

Background and Aims
Atherosclerotic plaque fluorine-18 sodium fluoride (18F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18F-NaF uptake.

Methods
Subjects with high CV risk but without CV events underwent 18F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20mg/daily for six months, and re-evaluated by 18F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation.

Results
Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years-old, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7±18.7% for ASCVD systems. After six months of rosuvastatin treatment (n=34), low-density lipoprotein cholesterol lowered from 133.6±33.8 to 58.8±20.7 mg.dL-1 (60% relative reduction, p&lt;0.01). There was a significant 19% reduction in maximum plaque 18F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p&lt;0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p=0.003).

Conclusion
In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18F-NaF uptake was significantly reduced after six months of high-intensity statin.Graphical abstractTrial design
Identification of new phenotypes in type 2 diabetes with acute myocardial infarction: toward a precision medicine?
Authors: Barbou A , Aho S , Boulin M , Adam H , Petit J M , Chague F , Bichat F , Zeller M , Cottin Y 
Published: October 2024

Abstract

Background
Type 2 diabetes mellitus (T2DM) is a highly heterogeneous entity, with multiple subgroups differing by clinic presentation, disease progression and risk of complications such as myocardial infarction (MI). A new T2DM phenotyping classification has been recently proposed to help to improve treatment tailoring and target early treatments, and we aimed to identify the prevalence and characteristics of the new phenotypes.

Methods
All consecutive adults with a history T2DM hospitalized in a french Coronary Intensive Care Unit for an acute MI between February 1st, 2021 and January 31st, 2023 were included. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of β-cell function and insulin resistance). We stratified patients into five subgroups : 1/ SAID=severe autoimmune diabetes; 2/ SIDD=severe insulin-deficient diabetes; 3/ SIRD=severe insulin-resistant diabetes; 4/ MOD=mild obesity-related diabetes; and 5/ MARD=mild age-related diabetes.

Results
Among the 266 patients included, characteristics according to diabetes phenotypes are summarized in the Table.

Conclusions
Our prospective study showed that in real-world T2DM patients with acute MI, unclassical phenotypes, i.e. hyperinsulinaemic and insulinopaenic were common. Given the large discrepancies in characteristics, our findings suggest the relevance of the new substratification. However, its clinical utlity and translation in tailored treatment strategies and prognosis remains to be determined.Table.
Adherence to a sustainable diet, measured via the EAT-Lancet Index, predicts incident short-term and long-term cardiovascular disease incidence: the ATTICA study (2002-2022)
Authors: Damigou E , Chrysohoou C , Barkas F , Vlachopoulou E , Vafia C , Dalmyras D , Adamidis P S , Kyrili K , Michelis E , Kravvariti E , Tsioufis C , Pitsavos C , Liberopoulos E , Sfikakis P P , Panagiotakos D B 
Published: October 2024

Abstract

Background/Introduction
The World Heart Federation has estimated that air pollution was the second most fatal modifiable risk factor for cardiovascular disease (CVD), causing approximately 5 million CVD deaths in 2021. Diets and food systems can affect the environment; however, research scarcely focuses on the association between planet-healthy dietary habits and CVD risk.

Purpose
The purpose of this study was to evaluate the adherence to a sustainable diet and CVD incidence during 20 years of follow-up.

Methods
Participants initially free-of-CVD from the ATTICA study were used (n=1,958). CVD events were assessed at baseline and at all follow-ups (i.e., 2002, 2012, 2022) according to WHO-ICD-10. Adherence to a sustainable diet was assessed via the EAT-Lancet Index (EAT-LI) (Education and Agriculture Together-EAT) (range: 0-42) based on the published algorithm.

Results
CVD incidence was 16.2% (n=317 incident cases) at 10-years and 35.3% (n=691 incident cases) at 20-years. Mean EAT-LI was: 17.3 (6.7) for the total sample. EAT-LI was lower in those that had a CVD event during the follow-up, i.e., EAT-LI: 10.5 (6.3) vs 18.5 (5.9) at 10-years (p&lt;0.001) and 10.9 (6.4) vs 20.8 (3.8) at 20-years (p&lt;0.001), in participants with and without a CVD event, respectively. In multi-adjusted analyses, adjusted for age, sex, body mass index trajectories, lifestyle trajectories, and clinical factors (diabetes, hypercholesterolemia, hypertension), higher adherence to a sustainable diet was inversely associated with CVD risk at a short-term and a long-term period (i.e., at 10 and 20 years). Specifically, per 1/42 increase in the EAT-Lancet index, CVD risk was reduced by 11% [Hazard ratio-HR: 0.89, 95%Confidence Interval: 0.86-0.93] and by 16% [HR: 0.84, 95%CI: 0.80-0.89] at 10 and 20 years, respectively.

Conclusion
Future guidelines for CVD prevention should take into account the sustainable nature of dietary habits, to efficiently nourish the growing world population, and concomitantly protect heart and planet health.
Cardiopulmonary exercise test findings are not the same in distinct types of cardiac amyloidosis
Authors: Santos Patarroyo S , Ortega-Aviles L , Grogan M , Allison T 
Published: October 2024

Abstract

Background
Cardiopulmonary exercise testing (CPET) is a widely used tool for risk stratification and prognosis in patients with chronic heart failure. In amyloid patients, cardiac amyloid deposits are associated with poor prognosis, increased risk for arrhythmias, sudden death, and subsequent exercise limitation due to restrictive cardiomyopathy. The type of amyloidosis and its affectation of the heart are different, and little is known about the CPET parameters according to the type of cardiac amyloidosis.

Purpose
In this study, we aim to compare CPET data in different types of amyloidosis to determine if CPET variables evaluated could have a significant difference that could impact the follow-up or prognosis of the patients based on the type of amyloidosis.

Methods
We conducted a retrospective cohort study of 194 patients with a diagnosis of cardiac amyloidosis referred for CPET from February 2010 to February 2024. Patients with at least one CPET data were included in our analysis. The type of amyloidosis, comorbidities, and echocardiogram data were retrieved from medical records. Patients were divided into 3 different groups according to the type of amyloidosis: AL Amyloidosis(AL), Variant TTR Amyloidosis (vTRR), and Wild Type TTR Amyloidosis (wtTTR). Individuals with CPET studies after heart transplant were excluded from the analysis. Fisher’s exact test or chi-square was used to compare categorical variables. ANOVA and Tukey-Kramer (TK) were used to compare continuous variables. Adjustment using General Linear Models (GLM) procedure was used to identify any confounder that could affect the results. A p-value &lt;0.05 was considered significant.

Results
Out of the 194 patients, 66 had AL Amyloidosis, 40 had vTTR Amyloidosis, and 88 had wtTTR Amyloidosis. Most of the patients were male, and the male predominance was higher in the wtTRR group. There were 41 (62.1%) males in the AL group, 35 (87.5%) in the vTRR group, and 83 (94.3%) in the wtTTR group (p&lt;0.0001). Comorbidities were balanced among the groups. Additional demographic and comorbidities data are shown in Table 1. From the evaluated CPET variables, VE/VCO2 nadir and slope were significantly higher in the wtTTR group when compared to the other groups, as well as Peak VE and Peak TV(Figure A). However, after adjusting for sex, BMI, and age, VE/VCO2 nadir was still significantly higher in the wtTRR group (p=0.003) compared to the other groups, as well as Peak VE, which was higher again in vTTR patients (p=0.001), and Peak TV (Table 2).

Conclusion
Ventilation variables evaluated in CPET showed alterations in the wtTTR group. These findings suggest that wtTRR amyloid patients could have a severe problem in ventilation that could be of significant relevance in future prognosis.
Unveiling a hide side of the athlete's heart: a CMR focus on the left atrium.
Authors: Monosilio S , Ferrera A , Ortolina D , Di Gioia G , Prosperi S , Lemme E , Netti L , Mango R , Tonti G , Pedrizzetti G , Gualdi G , Pelliccia A , Squeo M R , Maestrini V 
Published: October 2024

Abstract

Background
cardiac magnetic resonance (CMR) is the gold standard to evaluate cardiac chambers’ dimensions and function, but data on left atrium (LA) dimensions and function among elite athletes are lacking.

Objective
to describe LA size and function among a cohort of elite athletes and evaluate eventual differences based on sports discipline and gender.

Methods
We enrolled 120 Olympic athletes with un-remarkable cardiovascular pre-participation screening tests (mean age 25±5 years, 50% males, 25% skill, 25% power, 25% mixed, 25% endurance). All the athletes underwent CMR without contrast administration. LA dimensions, in terms of absolute and indexed area and volume, were computed using 4- and 2-chamber steady state precession cine-sequences. LA ejection fraction (LAEF) and LA coupling index (LACI index, as the ratio between LA and LV end-diastolic volumes) were calculated. Cine-images were also used to analyse atrial deformation with a dedicated offline software to measure LA global longitudinal strain. LA dimensions and function were compared between males and females and athletes of different sports categories based on European classification.

Results
Among the entire cohort, endurance athletes showed the greatest remodelling in terms of LA and LV dimensions (Table). There were no significant differences in LAEF and LV-EF between athletes of different sport categories (p=0.121 and p=0.679). A trend in increasing LA volumes and decreasing LA strain consistent with a growing cardiovascular demand was observed, but the only statistically significant difference was between skill athletes and all the other groups for LA volumes (p&lt;0.001), while there were no significant differences in LA strain (p=0.170). LACI did not differ between athletes of different sports categories (p=0.170). Female athletes showed higher LAEF and LA strain than males (respectively 55±5 vs 52±6% p=0.012 and 35±7 vs 32±7%, p=0.009) while LACI did not differ based on gender (19±5% for both females and males, p=0.385).

Conclusion
Among our cohort of Olympics, LA remodelling was observed in all athletes, being less evident in skill group, as for the LV. Thus, the ratio between LA and LV did not differ between sport categories. LAEF and LA strain were not significantly different between athletes of different sports categories although LA strain was slightly lower in endurance. Female athletes showed higher LAEF and LA strain than males, while LACI was not different based on gender.
Increased risk of cardiovascular events in the weeks following hospitalised COPD exacerbations: the EXACOS-CV French nationwide case-crossover study
Authors: Aboyans V , Nordon C , Poccardi N , Fabry-Vendrand C , Rhodes K , Rey A , Bretin O , Collin C , Zysman M 
Published: October 2024

Abstract

Introduction
Previous studies indicate that in people living with chronic obstructive pulmonary disease (COPD), the risk of myocardial infarction (MI), heart failure (HF) decompensation, arrhythmias and ischemic stroke increases following a COPD exacerbation. This association has not been explored for detailed types of cardiovascular events (CVE), namely for different types of myocardial infarction.

Objective
To quantify the risk of CVE following a COPD exacerbation overall, and by detailed type of CVE.

Methods
A case-crossover study was conducted using the French national hospital discharge database (Programme de Médicalisation des Systèmes d'Information, PMSI). Case-patients: (i) were aged≥40 years with a COPD diagnosis; (ii) hospitalised in 2018-2019 for CVE; (iii) experienced the CVE within 24 weeks of a hospitalised exacerbation of COPD. Hospitalisation date for CVE was index date. Conditional logistic regression models estimated the association between a hospitalised exacerbation and CVE (overall and by type of CVE) – expressed as odds ratios (OR) – comparing the odds of a hospitalised COPD exacerbation during the risk period (4 weeks prior to index date) versus control periods (9-24 weeks prior to index date).

Results
Among 122,172 patients with COPD hospitalised for a severe CVE in 2018-2019, 9,840 (8%) had a hospitalised exacerbation of COPD in the prior 24 weeks and qualified as case-patients. Mean age was 76.8 years (SD 10.7); 6,496 (66%) were male. The most frequent CVE were decompensated heart failure (n=5,888, 60%) and acute coronary syndrome (n=1,070, 11%); in-hospital death in the 24 weeks following an exacerbation of COPD occurred in 950 (10%) patients. Median time elapsed between hospitalised exacerbation and CVE (any type) was 43 days (Figure 1); the shortest delays were observed for non-STEMI (24 days) and resuscitated cardiac arrest (28 days). Risk of CVE in the 4 weeks following a hospitalised COPD exacerbation was 3-times the risk in the 9-24 weeks post-exacerbation (OR 3.0; 95%CI 2.9-3.2 – Figure 2). This increase in risk was observed for each individual type of CVE. The highest effect size was observed for non-STEMI (OR 5.3; 95%CI 4.5-6.3).

Conclusion
The risk of CVE substantially increases following a hospitalised exacerbation of COPD overall and for all types of CVE (acute ischemic events, arrhythmias, and heart failure decompensation). The first month following a hospitalised exacerbation is a period of vulnerability for people living with COPD, with some variability in the magnitude and temporality of risk increase according to the type of CVE. These results stress the need for immediate and sustained monitoring of exacerbating COPD patients to prevent a subsequent severe cardiac event. In addition, exacerbations prevention is an essential target of COPD treatment.
Prolonged ventricular repolarization acts as an independent predictor of sepsis prognosis: a cohort study and insights into intracardiac electrophysiology
Authors: Liu W , Shao R , Jin L , Zhang S , Liu R , Xiong N , Chen P , Ma H , Chen W , He B 
Published: October 2024

Abstract

Background
Sepsis-induced myocardial injury is a serious complication of sepsis, which requires identification in the early stage. The abnormality of ventricular repolarization is related to myocardial injury in a group of heterogeneous disorders. Prolongation of QT interval (QTP) is a proarrhythmic status reflecting the increased ventricular activation duration. However, the study on the clinical value of QT prolongation in sepsis and their potential mechanism is limited.

Purpose
We aimed to investigate the clinical characteristics, predictors of new-onset QT prolongation in sepsis and its relationship with outcomes in a multicenter cohort study, and exploration of the underlying mechanism of changes of ventricular repolarization in sepsis-induced myocardial injury.

Methods
Electrocardiograms were collected from septic patients after exclusion of QT-influencing medications and electrolyte abnormalities. The characteristics and predictive factors of QT prolongation (QTc&gt;450ms) were analyzed, and so was its impact on prognosis. Ventricular depolarization and repolarization were observed in lipopolysaccharide-treated mice with optical mapping. Bulk-RNA sequencing of septic myocardium and pathway enrichment were also performed. The ion channel-related gene expression was thereafter determined.

Results
QT prolongation occurred in 235/1024 (22.9%) patients from 4 centers. The majority demonstrated similar pattern as type I long QT syndrome. Patients with QT prolongation had a higher 15-day and 30-day in-hospital mortality (P&lt;0.001), which was demonstrated as an independent predictor for prognosis (P=0.044) after multivariate analysis. History of coronary artery disease (P=0.001), septic shock (P=0.008), acute respiratory (P&lt;0.001), heart (P=0.021) and renal dysfunction (P=0.013) were independent predictors of QT prolongation in sepsis. Optical mapping demonstrated longer QT interval and global action potential duration in lipopolysaccharide-treated mice without an increase in its dispersion within the ventricles. Sequencing of septic myocardium revealed significant downregulation of multiple potassium channel genes, consistent with the results of quantitative PCR.

Conclusion
New-onset QT prolongation in sepsis was associated with increased mortality as well as atrial and ventricular arrhythmias, which was predicted by disease severity and organ dysfunction. The prolongation of ventricular repolarization can be explained by the downregulation of potassium channel-related genes and the subsequent lengthening of activation potential duration.Graphic Abstract