bluuebunny/crossref_metadata_2025 huggingface dataset:
Percutaneous coronary intervention of in-stent restenosis: A three-arm analysis from SWEDEHEART
Authors: Von Koch S , Zhou M , Rosen H C , Zwackman S , Jurga J , Grimfjard P , Gotberg M , Mohammad M A , Erlinge D
Published: October 2024

Background

During the last decades, there have been substantial improvements in treatment techniques for percutaneous coronary intervention (PCI). Yet, in-stent restenosis (ISR) continues to pose significant challenges as they account for 10% of all PCI cases and are associated with worse outcome compared to de-novo lesions. When assessing ISR with PCI, balloon angioplasty with drug-coated balloons (DCB) is frequently used.

Purpose

Despite frequent use of DCB, there is a lack of long-term data ensuring the safety of DCB for ISR as no randomized trial has extended beyond a 3-year follow-up. We aimed to study the long-term outcome and conducted a nationwide three-arm investigation on the outcome of ISR, comparing DCB with drug-eluting stents (DES) or plain old balloon angioplasty (POBA) within a 5-year follow-up.

Methods

We conducted a nationwide analysis using the SWEDEHEART (Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry. The SWEDEHEART registry was used to include any ISR undergoing coronary angiography between June 11, 2013, and December 31, 2020. Target lesion revascularization (TLR) was the primary outcome. Secondary outcomes included all-cause mortality, myocardial infarction, and any PCI. The outcomes were analysed using a multivariable Cox regression model.

Results

A total of 9304 segments from 7987 patients were eligible. Compared to POBA, the use of DCB was associated with lower rates of TLR, hazard ratio (HR) 0.62 (95% confidence interval [CI]: 0.50-0.78), all-cause mortality, HR 0.60 (95% CI: 0.50-0.72), and any PCI, HR 0.78 (95% CI: 0.66-0.93). No difference was observed for myocardial infarction. Compared to DES, the use of DCB was associated with higher rates of TLR, HR 1.24 (95% CI: 1.08-1.42). No difference was observed for all-cause mortality, cardiovascular mortality, myocardial infarction, or any PCI.

Conclusions

In this nationwide analysis including any ISR undergoing PCI, the use of DCB showed superior outcomes compared to POBA within 5 years but higher rates of repeat revascularizations compared to DES. While DES demonstrated lower TLR rates than DCB, the lack of mortality differences indicates that DCB is a viable option, particularly for patients where DES might not be suitable, but that DES should be considered as the first line strategy.Table 1.5-year outcomeFigure 1.Kaplan-Meier curves
Impact of baseline thrombocytopenia on outcomes in hospitalizations for acute coronary syndrome and non-elective percutaneous coronary intervention: meta-analysis
Authors: Borra V , Mahadevan A , Vempati R , Kukkala S , Makwana B , Senapati S G , Jaiswal V
Published: October 2024

Background

Thrombocytopenia's impact on acute coronary syndromes (ACS) outcomes is poorly understood. A systematic review and meta-analysis aim to elucidate its influence on both short-term and long-term clinical endpoints, guiding tailored management strategies for improved patient care.

Methods

Our meta-analysis is registered on PROSPERO (CRD42024511832). We conducted a systematic search of PubMed and SCOPUS databases up to February 2024, utilizing keywords to identify studies on ACS or non-elective PCI populations with or without baseline thrombocytopenia (TP) reporting on in-hospital and long-term outcomes. Baseline TP was defined as a platelet count less than 150 x 10⁹/L and had to be established before hospitalization or ACS management or intervention. Binary random effects models were used to estimate pooled unadjusted odds ratios (OR) and 95% confidence intervals (CI). Sensitivity analysis was done by the leave-one-out method, and the heterogeneity was assessed with the I² statistics.

Results

From 2,831 identified studies, 10 were identified as eligible for inclusion in our pooled analysis and included 6,588,688 patients. Thrombocytopenia was associated with higher risks of in-hospital mortality (OR=1.89, 95% CI:1.55-2.30, p<0.01), in-hospital Major adverse cardiovascular events (MACE) (OR=1.99, 95% CI:1.63-2.43, p<0.01), and in-hospital bleeding (OR=2.62, 95% CI:1.89-3.64, p<0.01). Long-term follow-up revealed increased risks of MACE (OR=1.80, 95% CI 1.49-2.18, p<0.01), bleeding (OR=1.63, 95% CI:1.63-2.25, p<0.01), and cardiovascular mortality (OR=2.07, 95% CI:1.76-2.42, p<0.01) with thrombocytopenia. No significant difference was found in in-hospital stroke outcomes and long-term outcomes for stroke and recurrent myocardial infarction between thrombocytopenic and non-thrombocytopenic groups.

Conclusion

Thrombocytopenia worsens ACS outcomes. Vigilance and tailored management are crucial for mitigating its impact on patient prognosis. Further research is needed for better interventions.Secondary outcomes forest plot
Comparative outcomes of drug-coated balloon angioplasty versus second-generation drug-eluting stent for in-stent restenosis: a real-world data analysis
Authors: Krefting J , Krueger N , Graesser C , Schmieder R , Starnecker F , Kufner S , Cassese S , Kastrati A , Schunkert H , Von Scheidt M , Wiebe J
Published: October 2024

Background

Coronary in-stent restenosis (ISR) poses a significant challenge in interventional cardiology, with optimal treatment strategies being the subject of ongoing debate. Current clinical guidelines offer a choice between drug-coated balloon angioplasty (DCB) and repeat stenting with second-generation drug-eluting stents (DES), each with distinct implications for long-term patient outcomes.

Purpose

The aim of this study is to compare 1-year outcomes between DCB angioplasty and second-generation DES in the treatment of ISR. Longitudinal real-world data are used from the OBSERVABLE database, which comprises German health claims data between 2012 and 2021.

Methods

A total of 10,440 ISR individuals undergoing DCB or DES intervention were identified. After exclusion of bare-metal stents, first generation stents and non-DCBs, 3,810 propensity score-matched individuals remained. The primary outcome was the composite of all-cause mortality and myocardial infraction (MI). Secondary outcomes included all-cause death, MI, and bleeding as a safety outcome.

Results

At 1-year follow-up, the primary outcome of all-cause mortality and MI was observed in 246 individuals (12.9%) in the DES group, compared with 201 individuals (10.6%) in the DCB group (HR, 1.27; 95% CI, 1.06-1.53). Sensitivity analysis confirmed the robustness of these findings. Secondary outcomes revealed higher all-cause mortality in the DES group (7.9%) compared to the DCB group (6.3%) (HR, 1.31; 95% CI, 1.03-1.66), with no difference in MI. Bleeding events were comparable between the two treatments, with 244 individuals (12.8%) in the DES group and 206 individuals (10.8%) in the DCB group (HR, 1.17; 95% CI, 0.89-1.53).

Conclusion

This real-world data analysis demonstrated a higher incidence of the primary composite endpoint of all-cause mortality and MI within one year, after treatment with DES compared to DCB. Our results support prior findings about the safety profile of repeated DES implantation and strengthen DCB as a potential superior alternative to DES in ISR management.
CSWT improves ventricular function by promoting angiogenesis through Rho/ROCK/ERK1/2 signal pathway in infarcted myocardium in rats
Authors: Wang Y , Wang L U , Li C , Yang Y A N
Published: October 2024

Objective

This study aimed to investigate the effects of extracorporeal cardiac shock wave therapy (CSWT) on myocardial ischemia and cardiac function in rats with myocardial infarction, and to explore its impact on the expression of myocardial vascular endothelial growth factor and the extent of myocardial fibrosis, thereby elucidating the mechanism of angiogenesis.

Methods

A rat model of myocardial infarction was induced by ligating the left anterior descending branch of the coronary artery, confirmed by echocardiography. Animals were randomly assigned to five groups: sham operation group, myocardial infarction group, myocardial infarction + CSWT group, myocardial infarction + Y-27632 group, and myocardial infarction + CSWT + Y-27632 group. Cardiac function was evaluated by echocardiography on the 16th and 72nd day post-surgery. Myocardial morphology was assessed by HE staining, and the extent of myocardial fibrosis was determined by Masson's trichrome staining. Immunohistochemical staining for factor VIII was conducted to observe angiogenesis in each infarcted area. Western blotting was employed to detect the protein expression of extracellular regulated kinase (ERK1/2) and pro-angiogenic cytokines in the infarct border zone.

Results

CSWT treatment significantly reduced myocardial fibrosis and improved cardiac function compared to the myocardial infarction group. Additionally, CSWT upregulated ERK expression and angiogenesis-related factors, promoting angiogenesis. The beneficial effects of CSWT were abolished by inhibiting the Rho/ROCK/ERK1/2 pathway. Furthermore, the area of myocardial fibrosis was significantly reduced in the MI+Y-27632 group compared to the myocardial infarction group (p < 0.01), and left ventricular systolic function index was significantly higher in the myocardial infarction group.

Conclusions

CSWT may promote angiogenesis post-myocardial infarction by activating the Rho/ROCK/ERK1/2 pathway. Additionally, Y-27632 may improve cardiac function in rats with myocardial infarction, potentially through mitigating myocardial fibrosis.echo images of ratsprotein expression by WB
Efficacy and safety of Shexiang Baoxin pill in patients with ischemia with non-obstructive coronary arteries (LESS): a phase 4, multicenter, randomized, double-blind, placebo-controlled clinical trial
Authors: Liang C , Li N , He Z Q
Published: October 2024

Background

Patients with ischemia with non-obstructive coronary arteries (INOCA) present with ischemic signs and symptoms but no obstructive coronary artery disease (CAD) at coronary angiography. Shexiang Baoxin pill (MUSKARDIA) is effective in reducing angina frequency in patients with stable CAD.

Purpose

This phase 4 trial was conducted to evaluate the efficacy and safety of MUSKARDIA in INOCA patients.

Methods

This was a multicenter, randomized, double-blind, placebo-controlled clinical trial (NCT04897126). The enrolled patients with INOCA confirmed as eligible by leading PI were randomly assigned in a 1:1 ratio to receive MUSKARDIA or placebo (oral 4 pills 3 times a day) on the basis of conventional treatment until the end of follow-up. The primary endpoint was the angina-related outcomes based on the Seattle Angina Questionnaire (SAQ) score that assessed by same doctor at week 12.

Results

236 INOCA patients were randomized (MUSKARDIA group, n = 117; placebo group, n=119). At week 12, patients in MUSKARDIA group showed higher SAQ scores compared with placebo group (all P<0.0001, Figure 1) indicating MUSKARDIA could significantly relieve symptoms of angina. According to the Canadian Cardiovascular Society (CCS) grading of angina pectoris, the severity of angina pectoris was significantly reduced in MUSKARDIA group compared with placebo group at week 12 (grade Ⅰ [91.09% vs 48.15%]; grade Ⅱ [8.91% vs 25.93%]; grade Ⅲ [0% vs 19.44%]; grade Ⅳ [0% vs 6.48%]; P<0.001). After 12 weeks of treatment with MUSKARDIA, numbers of weekly angina attacks were significantly reduced compared with placebo group (-2.60 vs -0.42; LSM difference: -2.18; P<0.0001). The percentage of patients who did not used nitroglycerin was noticeably higher in MUSKARDIA group than that in placebo group (84.16% vs 58.33%, P<0.001). The incidence of adverse events did not differ meaningfully between two groups.

Conclusion

MUSKARDIA was confirmed to be an effective, safe and well-tolerated treatment for INOCA patients in clinical settings.
Clinical impact of Sarcopenia on long-term mortality in patients undergoing coronary bypass grafting
Authors: Lee S H , Jo J , Yang J H , Kim S M , Choi K H , Song Y B , Jeong D S , Lee J M , Park T K , Hahn J , Choi S , Cho Y H , Sung K , Kim W S , Gwon H
Published: October 2024

Background

Sarcopenia is an aging-related condition characterized by loss of skeletal muscle mass and is an indicator of subclinical atherosclerosis. The relationship between sarcopenia and long-term clinical outcomes in patients with advanced coronary artery disease who have undergone coronary artery bypass grafting (CABG) is not fully understood. This study aimed to evaluate the prognostic implications of sarcopenia in patients undergoing CABG.

Methods

A total of 2,810 patients who underwent CABG were derived from the Samsung Medical Center institutional registry from 2007 to 2017 and classified according to the presence of sarcopenia. The skeletal muscle index (SMI) was calculated as L3 muscle area (cm2)/height (m)2 on computed tomography. Sarcopenia was defined as SMI ≤45 cm2/m2 in men and ≤38 cm2/m2 in women. The primary outcome was all-cause mortality during follow-up.

Results

The median follow-up was 8.7 years, and 924 patients (32.9%) had sarcopenia. Patients with sarcopenia were older and more frequently women. SMI was significantly correlated with age (R=-0.34, P<0.001), weight (R=-0.56, P<0.001), and body mass index (R=-0.52, P<0.001). SMI was significantly associated with risk of death on a restricted cubic spline curve (HR=1.04 per-1 decrease, 95% CI 1.03-1.05, P<0.001). Patients with sarcopenia had a higher incidence of long-term mortality than those without sarcopenia (survival rate 41.4% vs. 62.8%; adjusted HR=1.18, 95% CI 1.03-1.36, P=0.02). Subgroup analysis showed that the prognostic implication of sarcopenia on long-term survival was more evident in men (adjusted HR=2.01, 95% CI 1.72-2.35) than women (adjusted HR=1.28, 95% CI 0.98-1.68) (interaction P=0.006).

Conclusions

Sarcopenia, defined by SMI on computed tomography, was associated with long-term mortality after CABG. These results provide contemporary data to allow the evaluation of physical frailty in patients with advanced coronary artery disease before surgery.
Sleep disordered breathing and in-hospital prognosis in acute myocardial infarction patients: a subset of the AMI-Sleep study
Authors: Balagny P , D'ortho M P , Sauze D , Rousseau A , Vidal-Petiot E , Drouet E , Gourmelen J , Durand-Zaleski I , Simon T , Steg P G
Published: October 2024

Background

Despite its high prevalence in patients with coronary artery disease (CAD), the association between sleep disordered breathing (SDB) and in-hospital prognosis is not well determined.

Purpose

We aimed to study in-hospital prognosis depending on the presence of SDB in patient hospitalized for acute myocardial infarction (AMI).

Methods

We prospectively enrolled a subset of patients hospitalized for AMI of the French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry included from January 2019 and December 2022 in the 16 AMI-Sleep-trained centers. Baseline and in-hospital information were collected through the FRENCHIE registry. A simplified polygraphy through ApneaLink Air+ was performed overnight during the initial hospitalization before discharge. Data were scored in centralized manner at a single center where trained physicians ascertained SDB severity based on Apnea-Hypopnea index (AHI). SDB screening was considered as positive for patients who have at least moderate SDB, defined by an AHI≥15/h.

Results

Among 1752 patients, 955 (54.5 [52.1;56.9] %) had at least moderate SDB. Compared with patients without SDB, SDB patients have major cardiac impairment including more 3-vessel CAD (26.8% vs 20.8%) and a lower admission left ventricular ejection fraction (52.2% vs 50.4%) associated with a higher use of non-invasive ventilation (3.8% vs 1.6% in non-SDB patients). SDB patients had also more in-hospital complications in particular more transfer to hospital intensive care (0.1% vs 0.9%) and an increased length of stay (4.8 vs 5.9 days).

Conclusion

More than half of the patients hospitalized for AMI had at least moderate SDB and presence of SDB was associated with more in-hospital morbidity. SDB screening should be considered to identify high risk sub-group of AMI patients.
Expression of cardiomyopathy-related genes in mononuclear blood cells predicts all-cause mortality in patients presenting with acute versus chronic coronary syndrome requiring revascularisation
Authors: Teren A , Beutner F , Scholz M , Holdt L M , Teupser D , Thiery J , Schuler G , Thiele H , Kirsten H
Published: October 2024

Objective

Despite advances in the revascularisation techniques their net clinical benefit differs substantially between patients presenting with myocardial infarction (ACS) and chronic coronary syndrome (CCS) due to obstructive coronary atherosclerosis.

Considering that leukocytes represents a key pathophysiological component of myocardial ischaemia, exploration of mononuclear blood cell (PBMC) gene expression profile in CCS and ACS setting could reveal clinically relevant transcriptomic signals. The aim of the present study was to identify differences in PBMC transcriptome between ACS and CCS patients which are linked to mortality after revascularisation.

Methods and Results

We analysed PBMC transcriptomes from719 ACS and 486 CCS patients creating discovery cohort. The results of transcriptomic analysis were verified in replication cohort (ACS: N=682 for CCS: N=489) generated based on propensity score matching. Median time from revascularisation to blood collection (IQR) was 15.68 (-4.52, 23.23) hrs. Patients with ACS showed consistent differential expression of 8173 genes (4544 upregulated, 3629 downregulated) when compared with CCS patients.

The subsequent pathway analysis also showed significant enrichment of several canonical pathways involved in major cardiovascular pathologies i.e. atherosclerosis (p = 1.22-06, enrichment = 3.39), vascular endothelial growth factor production (p = 1.16-06, enrichment = 16.73), positive regulation of vascular development (p = 2.78-06, enrichment = 5.30) and heterotopic cell adhesion including gene desmocollin 2 (DSC2, p = 3.64-04, enrichment = 6.30). In der multivariate survival analysis with differentially expressed genes, increased expression of DCS2, lamin A/C (LMNA), and UGGT2, and decreased expression of SNRNP70 predicted poor survival over the median follow-up 11.35 yrs. Consistently, controlling the false discovery rate at ≤ 5% these genes enriched pathways involved in cardiomyopathies such as arrhythmogenic right-ventricular cardiomyopathy (p = 4.19x10-4, enrichment = 58.9) and collagen disease (p = 2.29x10-3, enrichment = 23.8).

Conclusion

We found altered PBMC expression of multiple genes in patients requiring revascularisation for ACS versus CCS. Several differentially expressed genes included in cardiomyopathy pathways predicted long-term all-cause mortality in these patients.
Comparative analysis of vitamin K antagonists and direct oral anticoagulants for left ventricular thrombus management: a retrospective study utilising TriNetX
Authors: Yao Z , Gue Y
Published: October 2024

Introduction

Despite progress in cardiovascular medicine, guidelines for addressing left ventricular thrombus (LVT) remain limited. Furthermore, incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction (MI) adds complexity to treatment decisions. While conventional guidance favors vitamin K antagonists (VKAs), emerging evidence suggests favorable outcomes with direct oral anticoagulants (DOACs).

Purpose

This study aims to assess the safety and efficacy of DOACs versus VKAs in managing LVT among patients with and without recent acute coronary syndrome (ACS).

Methods

This was a retrospective observational study conducted within TriNetX, a global federated health research network with access to electronic medical records (EMRs) from participating health care organizations including academic medical centres and community hospitals covering approximately 70 million individuals, mainly in the United States. The search was conducted on 26th Februrary 2024 with a study cohort comprising patients with LV thrombus treated with either DOAC or VKA between 1st December 2013 to 1st December 2023. Subgroup analyses were conducted for patients with ACS within one month and those without ACS within a month of treatment. Cohort data were subject to propensity matching (PSM) for age, gender, ethnicities, medical and drug history. Risk analysis and Kaplan-Meier survival analysis were computed for each subgroup at 90 days since the indexed event.

Results

Following PSM, a total of 39,770 patients were included and 14,302 were in the ACS group and 24,162 in the non-ACS group. DOAC treatment exhibited favourable outcomes for stroke, bleeding, and systemic embolism (p<0.05) compared to VKA in the overall cohort (Table 1). In the ACS group, DOAC was linked to a reduced risk of stroke and systemic embolism (p<0.05) but not bleeding (p=0.066). In the non-ACS group, DOAC was associated with a decreased risk of stroke and bleeding (p<0.05) but not systemic embolism (p=0.113). Across all groups, there were no disparities in overall all causes of mortalities.

Conclusion

DOACs demonstrated better safety and efficacy outcomes when compared to VKAs in LVT treatment. Interestingly, DOACs utilisation within the ACS context resulted in a diminished risk of embolic complications without the benefit of reduced bleeding risk seen in patients without ACS, suggesting potential implications of triple therapy within first month of ACS treatment, removing the bleeding risk reduction of DOACs. This shows a fundamental difference in LVT between the 2 groups of patients so future studies should aim to differentiate between the 2.
Antithrombotic therapy in patients with atrial fibrillation after myocardial infarction and percutaneous coronary intervention
Authors: Skibniewski M , Venetsanos D , Zwackman S , Batra G , Janzon M , Karlsson L O , Alfredsson J
Published: October 2024

Background

Antithrombotic treatment with oral anticoagulants is recommended in clinical practice guidelines for patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) and concurrent atrial fibrillation (AF). Previous randomized controlled trials comparing warfarin and DOAC have primarily focused on bleeding complications. Consequently, the benefits and risks in an all-comer population remain uncertain.

Purpose

This study aimed to evaluate adherence to clinical practice guidelines within a large nationwide cohort and to compare outcomes among patients with MI and AF who were treated with dual antiplatelet therapy (DAPT), Warfarin, or DOAC.

Method

We utilized data from the nationwide SWEDEHEART registry to identify all patients with MI and AF between January 2010 and January 2021. We included all patients who underwent PCI and had a CHA2DS2-VASC score of ≥2 for men and ≥3 for women. The follow-up was one year. Patients were allocated into one of three antithrombotic treatment groups based on discharge medications: (1) Warfarin-based, (2) DOAC-based, and (3) DAPT only. The warfarin- and DOAC-based groups comprised patients on either dual or triple antithrombotic therapy. Study outcomes included: (1) major adverse cardiovascular events (MACE), defined as a composite of all-cause death, MI, or stroke; (2) net adverse cardiovascular events (NACE), which included MACE and bleeding complications; and (3) the individual components of MACE and NACE. Cox regression models were used to adjust for differences in baseline characteristics.

Results

Mean age among the 12,321 patients included was 76.1 years. At discharge, 3,563 (29%) were treated with warfarin, 3,671 (30%) received DOAC treatment, and 5,087 (41%) with DAPT alone. The percentage of patients treated with OAC increased from 30% in 2010 to 84% in 2021. Warfarin- and DOAC-based strategies were associated with lower MACE compared to DAPT alone, with adjusted hazard ratios [HR] (95% CI) of 0.77 (0.69-0.97) and 0.78 (0.69-0.90), respectively, as well as lower rates of NACE with adjusted [HR] (95% CI) of 0.84 (0.76-0.93) 0.84 (0.75-0.94), respectively. This difference was primarily driven by a difference in mortality, with adjusted ]HR] (95% CI) of 0.78 (0.67-0.91) and 0.80 (0.68-0.94), respectively. There were significantly fewer stroke events in the DOAC group (2.5 % vs 3.3%) compared with DAPT. No significant differences in bleeding events were observed between any of the treatment groups.

Conclusions

In this real-life retrospective study, we observed an increased utilization of guideline recommended OAC treatment over time. Both DOAC and warfarin treatment regimens were associated with a lower incidence of MACE and NACE compared to DAPT alone. No significant difference in outcomes were observed comparing DOAC vs Warfarin.
Nonalcoholic fatty liver disease worsens cardiac repair after myocardial infarction
Authors: Hamidou F , De Azevedo Laplace T , Duval V , Biquard L , Alayrac P , Achab Ali A , Lemitre M , Vilar J , Camus S , Rautou P E , Silvestre J S
Published: October 2024

Background

There is a strong epidemiological link between nonalcoholic fatty liver disease (NAFLD) and ischemic heart disease such as myocardial infarction (MI). Yet, a causal relationship between liver injury and post-MI cardiac repair remains to be established.

Purpose

NAFLD impairs post-MI myocardial repair processes. In particular, we hypothesized that the pathological liver could transmit deleterious signals shaping the inflammatory reaction in the infarcted milieu.

Methods

To characterize post-MI cardiac function and remodeling in three mouse models of liver damage mimicking different stages of NAFLD without cardiovascular (CV) risk factors : i) choline-deficient, L-amino-acid-defined, high fat diet (CDA-HFD) causing severe non-alcoholic steatohepatitis; ii) NEMOLPC-KO mice deficient for NF-κB in liver parenchymal cells, exhibiting liver inflammation and fibrosis, but mild steatosis; and ATGLLPC-KO animals deficient for Adipose Triglyceride Lipase in liver parenchymal cells displaying strong steatosis.

Results

In our three experimental models, liver damages were characterized by inflammation, steatosis and fibrosis but were not associated with metabolic syndrome. More interestingly, left ventricular ejection fraction were reduced by 1.2-fold, 1.3-fold and 1.3-fold in CDA-HFD, NEMOLPC-KO and ATGLLPC-KO male and female mice, respectively when compared to their respective controls, at 35 days post-MI (n=12-25 per group). NAFLD-induced cardiac dysfunction was not associated with worsen cardiac remodeling as infarct size, fibrosis and vascular density were not significantly affected. On the same note, flow cytometry experiments, at 7- and 14-days post-MI, showed no changes in the number or type of inflammatory cells, particularly that of cardiac resident macrophages, in CDAHFD, ATGLLPC-KO and NEMOLPC-KO mice. We next hypothesized that reduced left ventricular function could be induced by altered cardiomyocyte contractility. To corroborate this hypothesis, we isolated cardiomyocytes from hearts of infarcted mice with or without NAFLD and assessed cell contractility using IonOptix technology. Our preliminary results, in the CDAHFD model, showed that there was a reduction in contraction amplitude, defining by the ratio of the difference in sarcomere length during contraction/relaxation to the sarcomere length at the time of relaxation. The speed of contraction and relaxation were also decreased in CDAHFD mice compared with control animals.

Conclusions

NAFLD favors cardiac dysfunction post-MI. We now aim to identify molecular and cellular entities participating to such pathogenic dialogue between the dysfunctional liver and the infarcted heart.
Risk of recurrent ischaemic events in ACS patients with baseline LDL-C below guideline-recommended thresholds: insights from the prospective SPUM-ACS study
Authors: Denegri A , Kraler S , Wenzl F , Raeber L , Gencer B , Muller O , Nanchen D , Klingenberg R , Luescher T F
Published: October 2024

Introduction

The 2023 European Society of Cardiology (ESC) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with acute coronary syndromes (ACS), adding ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) to achieve recommended target goals (LDL-C<55 mg/dL).

Purpose

This population-based, real-world study aimed to examine cardiovascular (CV) events in ACS patients with baseline LDL-C levels below current guideline thresholds.

Methods

ACS patients admitted to four Swiss University Hospitals and enrolled in the multicenter SPUM registry (NCT 01000701) between 2009 and 2017 were followed prospectively until 1 year. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE); i.e., non-fatal stroke, myocardial infarction (MI), and death) at 1 year. Multivariable-adjusted Cox proportional hazard regression models were fit to estimate ischaemic risk among those with LDL-C<55 mg/dL.

Results

Out of 4’787 ACS patients, 226 patients (4.7%) had baseline LDL-C<55 mg/dL. These patients were older (69.7±11.3 vs 63.4±12.4, p<0.001), more frequently male (20.8%vs 15.9%, p<0.001), had more often traditional CV risk factors (all p<0.001) and were more likely to have a complex history of CV disease, such as previous MI (37.2% vs 10.9%, p<0.001), prior percutaneous (47.8% vs 13.2%, p<0.001) or surgical (15.0% vs 3.5%, p<0.001) coronary revascularization. Inflammatory biomarkers were also higher (hs-CRP, 30.1±63.6 vs 10.7±25.8 mg/L), with most patients being on high-dose statin therapy (82.4% vs 38.7%, p<0.001). At 1 year, patients with LDL-C<55 mg/dL had a higher rate of MACCE (16.4% vs 7.0%, p<0.001), with individual components of the primary endpoint occurring more frequently among these patients (all p<0.001), except for a numerical increase in CE (2.7% vs 1.7%, p=n.s.), as shown in the figure (Panel A). The enhanced MACCE risk persisted after adjustment for potential differences in baseline characteristics, with a 51% (adj. HR 1.51, CI95% 1.05-2.17, p=0.026) increase in MACCE (Panel B). Diabetes, low eGFR and high hs-CRP levels remained independent predictors of MACCE in patients with low baseline LDL-C (all p<0.001).

Conclusions

Our real-world data confirm that even ACS-patients reaching currently recommended LDL-C thresholds have a substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to further reduce CV risk.Event-risk according to baseline LDL-C
Causal association between visceral fat and coronary artery disease: a large-scale mendelian randomization analysis
Authors: Porcheddu T , Petretto G , Isgender M , Bilotta F , Merella P , Talanas G , Casu G , Navarese E P
Published: October 2024

Background

While increased body mass index (BMI) is an established risk factor, the residual risk associated with visceral fat, remains a concern. We aimed to perform a Mendelian randomization to explore the causal relationship between visceral fat and the risk of coronary artery disease (CAD), aiming to address gaps left by observational studies that may be influenced by confounding factors and reverse causation.

Methods

Leveraging large-scale genome-wide association study (GWAS) databases, we identified single-nucleotide polymorphisms (SNPs) associated with visceral fat. These genetic instruments were analyzed to infer causal relationships with CAD outcomes, drawing data from the CARDIoGRAMplusC4D consortium for CAD, and additional databases for related cardiovascular conditions. We performed a Two-sample Mendelian Randomization (MR) to test the genetic association between the visceral obesity and Coronary Artery Disease (CAD).

Results

The analysis encompassed data from a combined cohort exceeding 500,000 participants, revealing a significant causal relationship between increased levels of visceral fat and the risk of CAD. The observed odds ratio (OR) for CAD per standard deviation (SD) increase in visceral fat was [OR, 1.48 ] ([95% CI, 1.33-1.64]; P<0.001), indicating a robust association which remains independent from BMI on mediation analysis. Notably, the study's methodology ensured minimal risk of pleiotropy, reinforcing the validity of the findings.

Conclusions

This Mendelian randomization study provides compelling evidence of a genetic causal link between visceral fat and coronary artery disease. The findings suggest that beyond BMI, visceral fat represents a significant, independent risk factor for CAD, underscoring the importance of considering comprehensive lipid management in cardiovascular risk reduction strategies. Further research is warranted to explore potential mechanisms and therapeutic targets associated with visceral fat in the context of cardiovascular disease.
Impact of stress hyperglycemia ratio on periprocedural myocardial infarction in patients with NSTEMI
Authors: Asta C , Cavallo D , Suma N , Marinelli V , Casuso Alvarez M , Canton L , Fedele D , Bodega F , Pastore G , Ryabenko K , Bergamaschi L , Rinaldi A , Angeli F , Paolisso P , Pizzi C
Published: October 2024

Background

Stress hyperglycemia ratio (SHR), a new marker that reflects the true metabolic hyperglycemic state of patients regardless of the presence of diabetes mellitus, is strongly associated with adverse clinical outcomes in patients with acute myocardial infarction (AMI). However, studies on the impact of SHR on peri-procedural (type 4a) myocardial infarction (MI) are limited.

Purpose

The aim was to elucidate the relationship between SHR and type 4a MI in patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI).

Methods

We evaluated consecutive patients with NSTEMI, both diabetic and non-diabetic, who underwent PCI and exhibited stable (≤20% variation) or falling pre-procedure baseline cardiac troponin values and with sampled glycated hemoglobin available during hospitalization. Using receiver operating characteristic (ROC) curves, we categorized patients into two groups (higher SHR and lower SHR) based on the value associated with the highest Youden index. Subsequently, we assessed the incidence of type 4a MI in these two groups. Finally, we conducted Cox regression analyses to determine the independent prognostic impact of SHR on the risk of developing type 4a MI.

Results

We identified a threshold value of SHR=1.14 using ROC curves (AUC=0.684). The final study population comprised 837 patients with NSTEMI who underwent PCI, with 362 patients exhibiting SHR >1.14 at hospital admission. At baseline, patients with SHR >1.14 were older and had more comorbidities, including hypertension, diabetes, chronic kidney disease, and atrial fibrillation. Regarding coronary angiography and PCI characteristics, patients with higher SHR exhibited more frequent multivessel disease and consequently underwent more complex PCI procedures. Patients with SHR >1.14 developed type 4a MI more frequently than those with lower SHR (27.6% vs. 9.7%, p<0.001). Cox regression analysis demonstrated that, after adjusting for major comorbidities and complex PCI, the presence of SHR >1.14 at admission independently predicted a higher risk of type 4a MI after PCI in NSTEMI patients (OR=3.36; 95% CI 2.23 - 5.13; p<0.001). The adverse prognostic impact of higher SHR was further confirmed concerning in-hospital and long-term outcomes.

Conclusions

In patients presenting with NSTEMI undergoing PCI, elevated SHR (>1.14) at hospital admission is strongly associated with an increased risk of type 4a MI post-PCI, independent of major comorbidities and procedural complexity. These findings underscore the importance of SHR as a valuable prognostic tool in risk-stratifying patients with NSTEMI undergoing PCI, suggesting its potential utility for optimizing patient management strategies and improving clinical outcomes.
Impact of Lp(a) on lipid control in patients with acute coronary syndrome
Authors: Cesani N , Marchese A , Bocciolone M , Ammaturo T , Reimers B , Condorelli G , Panico C
Published: October 2024

Background

The lipoprotein(a) (Lp[a]) is a genetically determined low-density lipoprotein (LDL)-like particle. Lp(a) levels above 50mg/dl have been correlated to an increased risk of atherosclerosis and major adverse cardiovascular events. Thus, treatments designed to reduce Lp(a) levels are currently under investigation.

However, it is unknown how high Lp(a) concentrations affect the control of lipid profile.

Purpose

The purpose of this project is to investigate how Lp(a) impacts lipid profile control in individuals with acute coronary syndromes (ACS).

Methods

We designed a single-center prospective registry including consecutive patients admitted for ACS. Lp(a) levels were obtained from all enrolled patients during hospitalization; lipid profile (total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, triglycerides) was obtained at admission and at the 6-month follow-up (6MFU). Patients were stratified according Lp(a) concentration (low-Lp(a): Lp(a) < 50 mg/dL; high-Lp(a): Lp(a) ≥ 50 mg/dL). LDL-cholesterol (LDLcorr) levels corrected for concentration of Lp(a) were calculated as LDLcorr= LDLmeasured – 30%Lp(a). At discharge cholesterol lowering drugs were introduced or titrated as standard of care.

The primary endpoint was the percentage of patients reaching target LDL and LDLcorr (<55 mg/dL) at 6MFU.

The secondary endpoints were the correlations between Lp(a) levels and lipid profile, both at baseline and at 6MFU, as well as the correlation between Lp(a) levels and the total number of traditional cardiovascular risk factors in the study population.

Results

From February 2020 through September 2023, a total of 409 patients were included: 305 (74.6%) with Lp(a) < 50 mg/dL; 104 (25.4%) with Lp(a) ≥ 50 mg/dL (Table 1). High-Lp(a) patients showed a lower prevalence of diabetes (14.2% vs 27.87%, P = 0.0055), an overall lower number of traditional cardiovascular risk factors (>2 in 25.9% vs 38.1%, P=0.0244).

High-Lp(a) patients showed higher level of LDL-cholesterol compared to the low-Lp(a) population both at baseline (124±52 mg/dL vs 110.4±44 mg/dL, P= 0.0263) and at 6MFU (70.5±21 vs 63.8±29, P= 0.0208) with fewer patients achieving the target LDL cholesterol levels (21.57% vs 40.13%, P=0.0184).

Estimating the true LDL concentration (LDLcorr) the percentage of patients reaching target LDL cholesterol levels at FU significantly increased in the high-Lp(a) group (from 21.57% to 76.5%), with a minimal increase noticeable in the low-Lp(a) population (from 40.13% to 48.41%, p 0,1870).

Conclusions

In ACS population, patients with high Lp(a) concentrations have fewer traditional CV risk factors and a lower prevalence of diabetes. High-Lp(a) patients, furthermore, seem more challenging to meet LDL target at 6 month follow up, but not when the LDL values are adjusted for Lp(a).
Clinical and experimental evidence for differences between cardiac troponin I and T in acute and chronic cardiovascular conditions
Authors: Zimmermann T , Koechlin L , Walter J E , Lopez-Ayala P , Rentsch K , Strebel I , Diebold M , Twerenbold R , Lindahl B , Meex S , Mills N L , Marsano A , Hammarsten O , Mueller C
Published: October 2024

Background

Clinical and scientific practice operate under the assumption that systemic levels of cardiac troponin I (cTnI) and troponin T (cTnT) are indicative of the same underlying pathophysiological mechanisms and can be utilized interchangeably.

Purpose

To assess cTnI and cTnT levels and their ratio for differences in various cardiovascular conditions.

Methods

Individuals from three prospective clinical studies with a centrally adjudicated diagnosis were categorized into three groups: no known cardiac disease, chronic cardiac disease, and acute cardiac disease. Circulating cTnI and cTnT concentrations were measured using high-sensitivity assays (hs-cTnI-Architect, hs-cTnT-Elecsys) and the cTnI/cTnT ratio was calculated. Findings were validated using a second hs-cTnI assay (hs-cTnI-Clarity) and externally validated in independent cohorts. The cTnI/cTnT ratio was also assessed in five different non-lethal and lethal experimental models of cardiomyocyte injury.

Results

Of the 9704 included individuals, 9% had no known cardiac disease, 69% chronic cardiac disease, and 22% acute cardiac disease. No known cardiac disease and chronic cardiac disease were associated with a disproportional increase in cTnT compared to cTnI (cTnI/cTnT ratio, median 0.50, IQR 0.38-0.69 and 0.53, IQR 0.37-0.80). In contrast, cTnI concentrations were increased compared to cTnT in patients with acute cardiac disease, resulting in a cTnI/cTnT ratio of 1.62 (IQR 0.77-4.31).

Findings were consistent using an alternative cTnI assay and in external validation cohorts (n=2776) where the cTnI/cTnT ratio was lower in those without cardiac disease (0.33 (IQR 0.25-0.50), 0.64 (IQR 0.40-1.05)) and with chronic cardiac disease (0.50 (IQR 0.32-0.75), 0.60 (IQR 0.38-1.00)), compared to those with acute cardiac disease (2.22 (IQR 1.08-5.27), 2.28 (IQR 1.01-5.67)).

Non-lethal cardiomyocyte injury models showed a predominant release of cTnT with cTnI/cTnT ratios <0.5, and lethal injury models a predominant release of cTnI with cTnI/cTnT ratios >1.

Conclusion

Differences in cTnI and cTnT levels were observed in individuals with chronic and acute cardiac conditions, leading to distinct cTnI/cTnT ratios in both clinical and experimental settings. As a result, the interchangeability of cTnI and cTnT in present-day clinical and scientific settings needs to be reevaluated.Central illustration
Plasma levels of human growth differentiation factor 15 (GDF-15) and their effect of alirocumab on major adverse cardiovascular events and all-cause death after acute coronary syndrome
Authors: Jukema J , Van Neer N J , Szarek M , Cobbaert C , Bittner V A , Schwertfeger M , Bhatt D L , Fazio S , Garon G , Goodman S G , Harrington R A , Steg P G , Stevanovic I , White H D , Schwartz G G
Published: October 2024

Background

Human growth differentiation factor 15 (GDF-15) is a stress response cytokine of the transforming growth factor-β superfamily with roles in health and disease, cell survival and inflammation, and whose elevated plasma levels impair muscle metabolism and cause cachexia. GDF-15 also may play multiple roles in the pathophysiology of cardiovascular disease.

Methods

The ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab to placebo added to high-intensity or maximum-tolerated statin in patients post-acute coronary syndrome (ACS). We assessed in >11,000 patients for whom biobank samples were available, the relation between GDF-15 levels (Roche Diagnostics) at baseline and at 4 months with risk of major adverse cardiovascular events (MACE; primary endpoint, comprising coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischaemic stroke, unstable angina requiring hospitalization) and all-cause death, with adjustment for age and sex.

Results

Median GDF-15 (quartile [Q]1, Q3) at baseline was 1022 (755, 1465) pg/mL and was reduced by a placebo-adjusted median of 22 pg/mL with alirocumab (p=0.0009) at month 4. This lowering of GDF-15 by alirocumab may represent the first such report via pharmacotherapy. In the placebo group, baseline GDF-15 was significantly associated with risks of MACE (Figure Panel A) and death (Panel B). Relative risk reduction with alirocumab did not vary according to baseline GDF-15 levels for MACE (Panel C) and death (Panel D). Four-year MACE absolute risk reduction [ARR (95% CI)] with alirocumab at Q1 and Q3 of baseline GDF-15 was 2.0% (0.1%, 3.9%) and 2.6% (0.2%, 5.0%), respectively. Reduction of GDF-15 with alirocumab at month 4 was not associated with subsequent MACE (p=0.46) but was associated with death (p=0.0009), with greater reductions translating to lower risk.

Conclusion

In patients with recent ACS, GDF-15 is a strong predictor of both MACE and death. Reduction of GDF-15 with alirocumab at month 4 was not associated with subsequent MACE but was associated with death (p=0.0009), with greater ARR reductions translating to lower risk.

Figure. Splines for baseline GDF-15 vs risk of MACE (Panel A; spline p<0.0001) or all-cause death (Panel B; spline p<00001) through 4 years in the placebo group; treatment hazard ratio for MACE (Panel C; spline p=0.52) and all-cause death (Panel D; spline p=0.78). All splines reflect adjustment for age and sexFigure
Growth differentiation factor-15 and 5-years cardiovascular risk in chest pain patients presenting to the emergency department: a multicenter cohort study
Authors: Crisanti L , Lopez-Ayala P , Boeddinghaus J , Koechlin L , Nestelberger T , Bima P , Glaeser J , Spagnuolo C , Miro O , Martin Sanchez F J , Christ M , Mueller C
Published: October 2024

Background

Growth differentiation factor 15 (GDF-15) has been explored as a prognostic biomarker in multiple disease entities, including ischemic heart disease and heart failure (HF), but its role as a prognostic marker in chest pain patients presenting to the emergency department (ED) is unknown.

Purpose

To investigate the association between GDF-15 and 5-year all-cause mortality, cardiovascular mortality, and major adverse cardiac events (MACE), and to evaluate its prognostic incremental value.

Methods

Patients presenting to the ED with acute chest pain were prospectively enrolled in an international multicenter diagnostic study. GDF-15 concentrations were measured in a blinded fashion upon ED presentation. Follow-ups were performed at 3 months, 1-, 2- and 5-years. MACE was defined as the composite of cardiovascular mortality, acute myocardial infarction, stroke, and HF rehospitalization. Associations between GDF-15 and each prognostic outcome were modeled using multivariable Cox proportional hazard regression fitting restricted cubic splines to continuous variables. The magnitude of the effect of each GDF-15 unit change on multivariable-adjusted models was assessed graphically using dose-response plots. To compute an HR for the dose-response plots we chose a GDF-15 value of 1200 pg/mL as a reference value as this has been chosen in previous literature1. For the restricted cubic splines three knots were used. The added prognostic value of GDF-15 was evaluated by the increase in the C-statistic between a base and an extended model and the fraction of new information (FNI) provided by GDF-15.

Results

A total of 4779 chest pain patients had baseline GDF-15 values available. The median age was 61 [48-74] and 33% were female. Higher GDF-15 levels were more strongly associated with heart failure, kidney dysfunction, older age, hypertension, diabetes and coronary artery disease. GDF-15 was independently associated with 5-years all-cause mortality, cardiovascular mortality and MACE (Figure). When adding GDF-15 to a rich-for-prior-information base model which included age, sex, cardiovascular risk factors, creatinine, cardiac troponin and NT-proBNP, GDF-15 provided relevant incremental prognostic discrimination for 5-years all-cause death and cardiovascular death. (Table).

Conclusions

In chest pain patients presenting to the emergency department, GDF-15 concentration on admission was associated with 5-years all-cause mortality, cardiovascular mortality, and MACE. In addition, it provided relevant incremental prognostic information when added on top of troponin and NT-proBNP, the two current prognostic gold standard biomarkers.FigureTable