Events Myocardial Infarction Research Articles

Percutaneous coronary intervention versus coronary arterial bypass grafting in patients with left main coronary artery disease and chronic kidney disease: a systematic review and meta-analysis

Abstract Background Left main coronary artery disease (LMCAD), defined as a stenosis of >50%, is a potentially lethal condition that should be treated intensively by either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) depending on the anatomy. The presence of chronic kidney disease (CKD) complicates LMCAD, acting as a potential worsening factor for this group of patients, as well as impairing the effectiveness and outcomes of both revascularization treatments. Purpose This systematic review and meta-analysis aims to comprehensively compare the outcomes of PCI and CABG in patients with LMCAD and CKD. Methods A systematic search of the available literature was conducted in PubMed, Embase, and CENTRAL. Studies that compared PCI versus CABG in patients with LMCAD and CKD were included. The primary endpoints comprised major adverse cardiac and cerebrovascular events (MACCE) and all-cause death, while secondary endpoints included components of MACCE, such as myocardial infarction (MI), stroke and new revascularization events. The results were qualitatively and quantitatively synthesized and pooled hazard ratios (HR) were calculated. The statistical analysis was conducted in R. Results A total of 767 titles were initially retrieved, with five studies finally included in the analysis (n = 2,337 patients). The pooled analysis revealed that patients treated with PCI experienced more MACCE (HR: 1.50, 95% CI: 1.26-1.78, p < 0.001), an outcome primarily driven by MI (HR: 1.75, 95% CI: 1.17-2.62, p = 0.01) and revascularization rates (Hazard Ratio: 3.66, 95% CI: 1.84-7.30, p < 0.001), while no significant difference was shown in stroke rates (HR: 0.70, 95% CI: 0.40-1.22, p = 0.21). A trend towards increased all-cause death was observed for the PCI group, although this outcome slightly failed to reach statistical significance (HR: 1.30, 95% CI: 1.00-1.68, p = 0.05). Conclusion The present systematic review and meta-analysis indicated that PCI appears inferior to CABG in patients with LMCAD and CKD, with respect to most long-term outcomes. This includes higher rates of MACCE, and particularly MI and new events of revascularization for patients undergoing PCI, while all-cause death was marginally higher for this group. Further randomized controlled trials are needed to provide more robust evidence for guiding revascularization strategies in this high-risk population.

Short-term effects of ambient temperature variability on myocardial infarction hospitalizations in Sweden: A nationwide case-crossover study

Abstract Background Climate change threatens human health and general welfare via multiple dimensions. However, the short-term effect of temperature variability, a crucial aspect of climate change, on myocardial infarction (MI) remains largely unexplored. Purpose We aimed to assess the short-term effects of temperature variability on MI hospitalizations within the nationwide SWEDEHEART registry. Methods This population-based nationwide study involved 228,897 MI patients from the SWEDEHEART registry in Sweden from 2005 to 2019. High-resolution (1 km × 1 km) daily mean ambient temperature was estimated using a spatiotemporal machine learning methodology and assigned to patients’ home addresses. Temperature variability was calculated as the difference between the same-day (as the MI event) ambient temperature and the average temperature recorded over the preceding seven days. Specifically, an upward temperature shift represents a rise in the current day’s temperature relative to the seven-day average, while a downward temperature shift indicates a corresponding decrease. A time-stratified case-crossover design incorporating a conditional logistic regression model with distributed lag non-linear model was applied to estimate the association between ambient temperature variability and total MI, ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). Moreover, we assessed potential effect modification by sex and medication intake. The results were expressed as odds ratio (OR, with their 95% confidence intervals [CIs]) per 1°C increase in temperature variability. Results Our study found that a 1°C increase in upward temperature shift was significantly associated with increased risks for total MI, STEMI, and NSTEMI (OR [95% CI]: 1.010 [1.006-1.015], 1.014 [1.006-1.022], and 1.009 [1.004-1.014], respectively). Furthermore, a 1°C greater in downward temperature shift was significantly associated with decreased risks for total MI and NSTEMI (OR [95% CI]: 0.995 [0.991-0.999], and 0.993 [0.988-0.998], respectively). Moreover, we found that males and patients who were on any heart medication, particularly digitalis, were at a higher risk of MI associated with exposure to higher upward temperature shifts compared to females and their counterparts not taking these medications. Conclusions This nationwide case-crossover study provides novel evidence that short-term exposure to increasing upward temperature shift is associated with an increased risk of MI hospitalization. Our finding highlights the cardiovascular health threats posed by upward temperature shifts, which are anticipated to increase in frequency and intensity due to climate change.

Complement factor D deficiency ameliorates adverse cardiac remodelling by inhibiting C5a-C5aR mediated ISGs+ neutrophil activation post myocardial infarction

Abstract Background Exaggerated inflammatory response after myocardial infarction (MI) exacerbates myocardial injury and adverse cardiac remodeling, leading to heart failure. Current management of MI involves myocardial protection and antifibrotic therapy but do not target the inflammatory response per se. Complement factor D (CFD) is an upstream rate-limiting enzyme of complement system activation, which is the early event of inflammatory response post MI. We hypothesize that CFD can be an important modulator of the inflammation-remodeling cascade post MI, but the specific mechanism remains elusive. Purpose To investigate the role and mechanism of CFD in regulating inflammatory expansion and adverse remodeling post MI. Methods We generated Cfd-AKO (Cfdfl/fl Adipoq-cre) mice using the Cre-LoxP recombination system, as CFD is mainly secreted by adipocytes. Immune status and cardiac remodeling progress were assessed by cardiovascular magnetic resonance (CMR), histology, flow cytometry, immunofluorescence, and ELISA. Single cell RNA sequencing (scRNA-seq) analyzed non­cardiomyocytes isolated from Cfd-AKO and WT mice post MI or sham operation. Genetic ablation and co-culture experiments dissected the functional molecular properties and intercellular communication. An CFD inhibitor ACH-4471 was used to explore the role of CFD in ischemia-reperfusion (IR) injury. Results The survival of Cfd-AKO mice was strongly improved, while ventricular arrhythmia induction rates and number of episodes were significantly reduced compared with those of WT mice. CMR imaging showed that Cfd-AKO mice had higher ejection fraction and reduced left ventricular dilation than WTs. Masson trichrome and picrosirius red staining revealed that besides smaller infarct size, the extent of fibrosis in the border and distal remote area decreased in Cfd-AKO mice. Cfd loss reduced myocardial injury, inhibited the release of inflammatory factors, and limits the amplification of complement components C3a and C5a post MI. ScRNA-seq revealed that CFD modulated neutrophil chemotactic ability and pro-inflammatory function by inducing interferon-stimulated genes expressing (ISG+) neutrophil CXCL10 expression. Mechanistically, CFD activates the ISG transcriptional profile via the C5a/C5aR dependent STAT1/2-IRF9 pathway. Activated neutrophils promote myofibroblast transformation through IL1β/IL1R dependent intercellular communication, thus facilitating pathological fibrosis. Early pharmacological blocking of CFD in mice IR injury models inhibited inflammation, reduced infarct size and ameliorated cardiac dysfunction. Conclusions We demonstrate the crucial role of CFD in cardiac remodeling post MI. This process is critically regulated by C5a-C5aR, an important component of complement-inflammation cascade. This CFD-C5a mediated neutrophil pro-inflammatory and pro-fibrotic dual activity represents a novel pathway and an attractive therapeutic window for heart failure post MI.CFD in cardiac remodelling post MI

Effects of deferment of clinic visit on cardiovascular outcomes during COVID-19 outbreak: a prospective cohort study

Abstract Background Current guidelines recommend 3-6 months interval outpatient follow-up for patients with cardiovascular (CV) diseases and risk factors such as hypertension, diabetes mellitus (DM) and dyslipidemia. The impact of longer follow-up intervals is unclear. From 2020 to 2022, due to the infection control measures for COVID-19 pandemic, many patients voluntarily deferred their scheduled clinic visits. This provided us with an opportunity to study the impact of prolonged visit intervals on management CV risk factors. Purpose We aimed to investigate the impact of prolonged clinic visit intervals on CV outcomes and CV risk factor management among patients with CV diseases. Methods Patients with at least 1 CV risk factor (DM, hypertension, dyslipidemia, or a history of CV disease) were recruited from cardiology outpatient clinics from a tertiary teaching hospital from 2020-2022. Patients who opted to defer their appointment (Deferred group) were compared to those who attended their scheduled appointment (Normal group). The primary outcomes were composite major adverse cardiovascular events (MACE) of myocardial infarction, stroke, or CV-related death. The secondary outcomes were any unscheduled hospitalizations, suboptimal DM control (haemoglobin A1C >7%) or hyperlipidemia (LDL > 1.4 mmol/L). Results Out of the 455 patients recruited from outpatient clinics, 162 patients (35.6%) opted to defer their scheduled clinic visit (mean age 64.7 ± 12, 37.7% female), and 293 patients (mean age 64.5 ± 10, 36.2% female) continued to attend their appointments. The mean appointment interval was 226 days for the normal group and 582 days for the deferred group (p< 0.001). There was no significant difference in the primary outcome of MACE between the ‘Normal’ group and the ‘Deferred’ group (2.5% vs 0.6%, p=NS). The number of patients with suboptimal DM control (11.4% vs 21.9%, p = 0.029) was higher in the deferred group, whereas suboptimal hyperlipidemia (73.1% vs 77.1%, p=NS) was not statistically different. There were a total of 27 of unscheduled hospitalizations, among which the majority was for CV-related events (63.0%). Patients in the ‘Deferred’ group had higher rates of unscheduled hospitalization (12.3% vs 2.4%, p < 0.001) and higher rate of CV-related hospitalization compared to the ‘Normal’ group (6.2% vs 2.4%, p=0.041). Conclusion Our prospective data demonstrates that a prolonged clinic visit interval of more than 365 days was not associated with significant increase in adverse CV event or worsening of lipid control. However, prolonged clinic visit interval was associated with worse DM control and more frequent unscheduled hospitalization. More frequent medical contact might allow timely management of medical emergency at the outpatient setting and contribute to the lower rate of hospitalization in the routine follow-up group.

Impact of the complexity of percutaneous coronary intervention on clinical outcomes in patients with atrial fibrillation: a real-world study

Abstract Background Atrial fibrillation (AF) always coexisted with percutaneous coronary intervention (PCI), and complex PCI has increased in recent years. However, limited data exist on clinical outcomes in patients with AF and underwent complex PCI. Purposes We aimed to explore the prognosis of patients with AF who had underwent PCI. Methods This was a prospective, observational study which enrolled 1132 participants consecutively. Complex PCI was defined as PCI performed to ≥ 3 separate major coronary vessels; ≥3 stents implanted; ≥3 lesions treated; or total stented > length 60 mm. The primary endpoint was defined as major adverse cardiovascular event (MACE) including all-cause death, spontaneous myocardial infarction (MI), stroke, systemic embolism or ischemia-driven revascularization. Major bleeding events were defined according to Thrombolysis in Myocardial Infarction (TIMI) criteria. Results A total of 1132 patients who underwent PCI with AF were enrolled. The mean age was 66.6 ±8.9, and 75.1% were male. 320 participants (28.2%) were undergoing complex PCI. During a median follow-up of 1045 days, the primary outcome occurred in 52 of 320 patients (16.2%) in the complex PCI group and 105 of 812 patients (12.9%) in the non-complex PCI group (adjusted hazard ratio: 1.31; 95% confidence interval: 1.08-1.58; P = 0.007), driven by higher rate of MI ( aHR=2.17, 95%CI, 1.00-4.70 and ischemic driven revascularization (aHR=1.86, 95%CI, 1.01-3.45). TIMI major bleeding events were more commonly observed in complex PCI group (aHR=1.15, 95%CI, 1.01-1.31). Conclusion The complexity of PCI was an independent risk factor of adverse clinical outcomes, especially in MI, revascularization and TIMI major bleeding events in patients with AF.K-M curves of eventsK-M curves of events

Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: implications of insulin treatment: a report from the GLORIA-AF Registry Phase III

Abstract Background Atrial Fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations has not been fully elucidated, especially in relation to insulin use. Purpose To analyze the associations between DM and the risk of clinical adverse events in patients with AF, and second, explore the impact of insulin treatment in these patients. Methods We studied patients with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-years follow-up. Clinical events included all-cause death, major bleeding, myocardial infarction (MI), stroke, thromboembolism (TE), and major adverse cardiovascular events (MACE). MACE was defined as a composite of stroke, MI and major bleeding. Kaplan-Meier curves were used to estimate the cumulative incidence of clinical events. Multivariable cox regression models with subgroups were used to estimate the association between DM and the risk of mortality and clinical events. Results A total of 15,861 AF patients were included (mean age 70.00 ± 10,21 years old; 55% male, 20% Asia), of which 3,666 had DM (mean age 70.04 ± 9.54 years old; 59% male, 21% Asia). Kaplan-Meier curves showed that AF patients with DM had higher cumulative hazard of all outcomes, including all-cause death (OR: 1.56, 95%CI: 1.38-1.77), CVD (OR: 1.72, 95%CI: 1.44-2.06), major bleeding (OR: 1.4, 95%CI: 1.17-1.67), stroke (OR: 1.29, 95%CI: 1.04-1.61), TE (OR: 1.26, 95%CI:1.02-1.56), MI (OR: 1.88, 95%CI: 1.48-2.39) and MACE (OR: 1.61, 95%CI: 1.41-1.84). After adjustment by prior disease and drugs, the outcomes of stroke (OR: 1.19, 95%CI: 0.95-1.49) and TE (OR: 1.22, 95%CI: 0.98-1.52) showed not significant. Subgroup analysis found that increased risks of stroke were found in female (OR: 1.43, 95%CI: 1.03-1.98, Pinteraction = 0.062) and non-Asian patients (OR: 1.39, 95%CI: 1.06-1.82, Pinteraction = 0.175) with DM. For all cause death, subgroup results were similar with overall patients. In addition, insulin use increased the risk of all cause death (OR: 1.82, 95%CI: 1.45-2.29), CVD (OR: 1.70, 95%CI: 1.22-2.37), major bleeding (OR: 1.54, 95%CI: 1.08-2.18), MI (OR: 1.72, 95%CI: 1.12-2.64), MACE (OR: 1.65, 95%CI: 1.28-2.11) in patients with AF and DM. Multivariable model showed similar result. Conclusions DM was independently associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF. Insulin use was associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF and DM.Figure 1Figure 2

Correlation analysis of self-rated health and net adverse clinical events in patients with acute myocardial infarction

Abstract Backgrounds Self-rated health (SRH） is a recognized standard risk factor for myocardial infarction, but its impact on prognosis remains uncertain. Purpose This study aims to investigate the impact of self-rated health on the long-term clinical outcomes of myocardial infarction patients. Methods The data for this study were derived from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023, Patients were divided into satisfied and unsatisfied groups based on their responses to an SRH questionnaire. Propensity score matching (PSM) was utilized to balance covariates between the two groups and analyze the relationship between SRH and clinical outcomes. The primary endpoint was net adverse clinical events (NACE), comprising cardiac death, recurrent myocardial infarction, revascularization, ischemic stroke, and bleeding events (BARC ≥3). The secondary endpoint comprised the individual components of the primary endpoint. Results The study included a total of 55,054 AMI patients, with 54,049 rating their health as satisfactory and 1,005 patients as unsatisfactory. In the satisfactory group, patients tended to be younger, had fewer females, better Killip classification, a higher proportion of STEMI cases, a higher rate of undergoing PCI, and a lower prevalence of concomitant disease such as diabetes, hypertension, chronic kidney disease, cerebrovascular disease, peripheral vascular disease, thyroid disease, and chronic lung disease. Additionally, patients in the satisfactory group had a higher proportion of antiplatelet therapy use (aspirin, ticagrelor). 1,005 pairs were well matched after PSM. After a median follow-up of 1626 days, the proportion of all-cause death, cardiac death, and recurrent myocardial infarction in the satisfied group was significantly lower than that in the unsatisfied group. Multivariable Cox regression analysis revealed that satisfactory SRH was associated with a reduced risk of NACE (aHR 0.809, 95%CI 0.704-0.930, P=0.002), cardiac death (aHR 0.790, 95%CI 0.665-0.939, P=0.007), and recurrent myocardial infarction (aHR 0.734, 95%CI 0.563-0.955, P=0.021). Conclusions Good SRH can decrease the risk of NACE in myocardial infarction patients, underscoring the importance of considering SRH in clinical assessment.

The incidence of death and risk factors for mortality following major bleeding in patients anticoagulated with factor Xa inhibitors: an observational study in the UK clinical setting (AXIOM UK)

Abstract Background Major bleeding (MB) in association with anticoagulant use results in significant mortality. Mortality can be directly attributed to bleeding, or may follow bleeding complications such acute kidney injury, myocardial infarction, stroke and other cardiovascular events. Most real-world data relating to bleeding mortality is derived from cohorts receiving vitamin-K antagonists. We investigated all-cause mortality (ACM) after MB in a large cohort anticoagulated with Factor Xa inhibitors (FXai), e.g. direct oral anticoagulants (DOAC) rivaroxaban, apixaban and low-molecular-weight heparins (LMWH). Purpose To describe incidence rates of and risk factors for ACM following MB in patients receiving FXai. To investigate MB related ACM by bleeding site, treatment indication, treatment subgroups and individual and cumulative time periods. Methods Retrospective cohort analysis of new users of FXai, between 2012-2020, for therapeutic indications including atrial fibrillation (AF), venous thromboembolism, bioprosthetic cardiac valves or adult congenital heart disease was conducted. MB was defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Incidence rates were reported per 100 person-years. Sub-distribution hazard ratios with 95% confidence intervals (95% CI) were estimated from Fine and Gray regression models accounting for competing risks. Results In 240,357 new users of FXai, 88% used an oral FXai. The most common FXai indication was AF (72%). There were 10,163 patients (4.2%) hospitalised for bleeding events during FXai use. Of these, 3,873 MB events (38%) fulfilled the ISTH definition of MB and 1312 died during 3,542 person years of follow-up (Table 1). ACM incidence rates varied by time, indication, bleeding subtype, and drug type. ACM occurred in 926 patients (23.9%) in the first month. Mortality rates were highest in the first month 607 (95% CI 568-647) per 100 person years, the rates then decreased over the year but remained elevated throughout the first year compared with subsequent years. Those receiving LMWH had higher ACM than those receiving a DOAC, but this was not significant in the adjusted risk factor analysis. Risk factors for ACM following bleeding included age ≥80, and a history of current smoking, myocardial infarction, congestive heart failure, peripheral artery disease, Stage 4 or 5 kidney disease, metastatic cancer, and intracranial haemorrhage. Age<60, bleeding following major trauma, and a history of anaemia were associated with lower risk of ACM (Table 2). Conclusions There is a significant incidence of ACM following MB among FXai users. The incidence rate of ACM in patients treated with FXai was highest in the first month after FXai initiation, declined during the first year and then plateaued. Multiple risk factors associated with ACM have been recognised and these could guide urgent therapies such as antidotes.

Free-Cell Area Impact on Stroke Prevention in Asymptomatic Patients Undergoing Carotid Artery Stenting: The "Carotid Artery sTenting And CeLl-area Impact on Stroke and Major Adverse events" (CATACLISMA) Multicenter Registry.

The study investigated the association between cell-stent area and cerebrovascular events incidence in asymptomatic patients undergoing carotid artery stenting (CAS). This is an observational, retrospective, multicenter, cohort study. Between 2012 and 2022, all patients undergoing primary CAS for severe asymptomatic carotid artery stenosis were evaluated. Three groups were defined on the basis of the cell area (open cell, OC; closed cell, CC; double layer, DL). Periprocedural primary outcomes were 30-day stroke, mortality, myocardial infarction (MI), and major adverse event (MAE, stroke/mortality composite outcome) rates. Follow-up primary outcomes included overall survival, stroke-free survival (SFS), freedom from ipsilateral stroke (FFiS), and freedom from stroke-related mortality (FF-SRM). Data were analyzed at short-term (1 year) and mid-term (2.5 years) period. A total of 1096 CAS were considered (787 men, 71.8%, median age = 74 years). Technical success was achieved in 99.5% procedures. Periprocedural 30-day stroke rate was 1.5% (OC: 1.1%, CC: 2.3%, DL: 1%, p=0.27), mortality was 0.7% (OC: 1.1%, CC: 0.3%, DL: 0.5%, p=0.35), and no MI was recorded. The MAE rate was 2.1% (OC: 2%, CC: 2.6%, DL: 1.5%, p=0.66). Median follow-up was 46 months. At 1 and 2.5 years, estimated overall survival was 96.1% and 91% (p=0.41), SFS was 99.1% and 98.2% (p=0.007, CC stroke rates 2.9% and 4.2% at timepoints), FFiS was 99.4% and 99% (p=0.014, CC FFiS rates 1.7% and 2.6% at timepoints) and FF-SRM was 99.5% and 99% (p=0.28). During follow-up, no stroke events occurred in DL group. CC design showed higher rates of any (4.2%) and ipsilateral stroke (2.6%) within 2.5 years. In asymptomatic patients undergoing CAS, the contemporary overall stroke incidence is 1.5%. No statistical differences were observed in terms of 30-day stroke incidence among groups. The closed free-cell area showed higher rates of any and ipsilateral stroke within 2.5 years. The DL stents may offer the best available performances in terms of mid-term stroke prevention. The study analyzed the contemporary results of carotid artery stenting (CAS) focusing on the impact of cell-stent area on peri- and post-operative cerebrovascular events in a multicenter real-world experience. In asymptomatic patients undergoing CAS the contemporary overall stroke incidence is 1.5%. No statistical differences were observed in terms of 30-day stroke incidence among groups. The closed free-cell area showed higher rates of any and ipsilateral stroke within 2.5 years. DL stents may offer the best available performances in terms of mid-term stroke prevention.

Metformin's cardioprotective role in isoprenaline-induced myocardial infarction: Unveiling insights into the AMPK, NF-κB, JAK2/STAT3 pathways, and cholinergic regulation

AimDespite advancements in treatment modalities, myocardial infarction (MI) remains a significant global cause of mortality and morbidity. Metformin (MET), a commonly used antidiabetic medication, has demonstrated potential in various cardioprotective mechanisms. This study investigated whether MET could alleviate the histopathological, electrocardiographic, and molecular consequences of MI in rats. Materials and methodsThe study hypothesis was tested using an isoprenaline (ISOP)-induced MI model, where male Wistar rats were injected with ISOP (85 mg/kg/day, s.c., for 2 days) and treated with MET at the doses of 500 and 1000 mg/kg/day for 18 days or left untreated. Key findingsISOP-treated rats exhibited several indicators of MI, including significant ST-segment depression and prolonged QT-intervals on ECGs, worsened left ventricular histopathology with increased inflammatory cell infiltration, reduced expression of cardiac CHRM2, a cardioprotective cholinergic receptor, adaptive increases in AMPK and α7nAchR levels, and elevated levels of iNOS, NO, STAT3, JAK2, IL-6, TNF-α, and NF-κB. These effects were attenuated in rats treated with either low or high doses of MET. MET administration restored normal ECG recordings, diminished oxidative stress and inflammatory mediators, and downregulated NF-κB expression. Moreover, MET improved CHRM2 expression and normalized α7nAchR levels. Additionally, MET influenced the expression of key signaling molecules such as Akt, STAT3, and JAK2. SignificanceThese findings might suggest that MET exerts cardioprotective effects in ISOP-induced MI in rats by mitigating critical inflammatory signaling pathways and regulating protective cholinergic mechanisms in the heart.

Cardiomyocyte-derived C-type natriuretic peptide diminishes myocardial ischaemic injury by promoting revascularisation and limiting fibrotic burden

BackgroundC-type natriuretic peptide (CNP) is a significant player in the maintenance of cardiac and vascular homeostasis regulating local blood flow, platelet and leukocyte activation, heart structure and function, angiogenesis and metabolic balance. Since such processes are perturbed in myocardial infarction (MI), we explored the role of cardiomyocyte-derived CNP, and pharmacological administration of the peptide, in offsetting the pathological consequences of MI. MethodsWild type (WT) and cardiomyocyte-restricted CNP null (cmCNP-/-) mice were subjected to left anterior descending coronary artery (LADCA) ligation and acute effects on infarct size and longer-term outcomes of cardiac repair explored. Heart structure and function were assessed by combined echocardiographic and molecular analyses. Pharmacological administration of CNP (0.2 mg/kg/day; s.c.) was utilized to assess therapeutic potential. ResultsCompared to WT littermates, cmCNP-/- mice had a modestly increased infarct size following LADCA ligation but without significant deterioration of cardiac structural and functional indices. However, cmCNP-/- animals exhibited overtly worse heart morphology and contractility 6 weeks following MI, with particularly deleterious reductions in left ventricular ejection fraction, dilatation, fibrosis and revascularization. This phenotype was largely recapitulated in animals with global deletion of natriuretic peptide receptor (NPR)-C (NPR-C-/-). Pharmacological administration of CNP rescued the deleterious pathology in WT and cmCNP-/-, but not NPR-C-/-, animals. Conclusions and implicationsCardiomyocytes synthesize and release CNP as an intrinsic protective mechanism in response to MI that reduces cardiac structural and functional deficits; these salutary actions are primarily NPR-C-dependent. Pharmacological targeting of CNP may represent a new therapeutic option for MI.

Exposure to Air Pollutants and Myocardial Infarction Incidence: A UK Biobank Study Exploring Gene-Environment Interaction.

Unraveling gene-environment interaction can provide a novel insight into early disease prevention. Nevertheless, current understanding of the interplay between genetic predisposition and air pollution in relation to myocardial infarction (MI) risk remains limited. Furthermore, the potential long-term influence of air pollutants on MI incidence risk warrants more conclusive evidence in a community population. We investigated interactions between genetic predisposition and exposure to air pollutants on MI incidence. This study incorporated a sample of 456,354 UK Biobank participants and annual mean air pollution (, , , and ) from the UK Department for Environment, Food and Rural Affairs (2006-2021). The Cox proportional hazards model was employed to explore MI incidence after chronic air pollutants exposure. By quantifying genetic risk through the calculation of polygenic risk score (PRS), this study further examined the interactions between genetic risk and exposure to air pollutants in the development of MI on both additive and multiplicative scales. Among 456,354 participants, 9,114 incident MI events were observed during a median follow-up of 12.08 y. Chronic exposure to air pollutants was linked with an increased risk of MI occurrence. Specifically, the hazard ratios (per interquartile range) were 1.12 (95% CI: 1.10, 1.13) for , 1.20 (95% CI: 1.19, 1.22) for , 1.13 (95% CI: 1.12, 1.15) for , and 1.12 (95% CI: 1.11, 1.13) for . In terms of the joint effects, participants with high PRS and high level of air pollution exposure exhibited the greatest risk of MI among all study participants ( to 324%). Remarkably, both multiplicative and additive interactions were detected in the ambient air pollutants exposure and genetic risk on the incidence of MI. There were interactions between exposure to ambient air pollutants and genetic susceptibility on the risk of MI onset. Moreover, the joint effects of these two exposures were greater than the effect of each factor alone. https://doi.org/10.1289/EHP14291.

Statin use is associated with less ST-elevation versus non-ST-elevation myocardial infarction in a nationwide study

Background and aimsStatin therapy reduces myocardial infarction rate but whether it is associated with a shift of ST-elevation myocardial infarction (STEMI) towards non-ST-elevation myocardial infarction (non-STEMI) remains unknown. Thus, we tested the hypothesis that statin use is associated with less STEMI relative to non-STEMI in first-time myocardial infarction. MethodsIn a nationwide study, including 66896 patients with first-time myocardial infarction between 2010 and 2021, we obtained multivariable risk estimates for STEMI versus non-STEMI according to any statin use, cumulated statin use, and daily statin dose. Furthermore, we obtained hazard ratios for 60-day mortality (5545 deaths) following myocardial infarction according to type of infarction. ResultsOdds ratios for STEMI versus non-STEMI were 0.81 (95% CI:0.77-0.85) and 1.07 (1.01-1.13) in current and previous statin users compared to never statin users. Cumulated statin exposure yielded odds ratios of 0.96 (0.87-1.07) for <2 statin-years, 0.87(0.79-0.95) for 2-4.9 statin-years, 0.80 (0.74-0.87) for 5-10 statin-years, and 0.75(0.70-0.80) for >10 statin-years compared to never users. Corresponding odds ratios for statin dose intensity were 0.89 (0.84-0.95) for low-intensity, 0.77 (0.73-0.82) for moderate-intensity, and 0.70 (0.63-0.77) for high-intensity. Results were similar in multiple sensitivity analyses and using a cohort design. The hazard ratio for 60-day mortality after first-time STEMI versus non-STEMI was 2.24 (2.13-2.37). ConclusionsIn this nationwide study, prior statin use is associated with less STEMI relative to non-STEMI in a dose dependent manner. This indicates that statin therapy, in addition to reducing myocardial infarction event rates, also result in a less severe presentation of myocardial infarctions.

Multicenter retrospective cohort study demonstrates superior safety profile of indobufen over aspirin for Post-CABG antiplatelet therapy.

Coronary artery bypass grafting (CABG) is essential for treating coronary artery disease, with postoperative aspirin crucial to prevent graft restenosis. However, its gastrointestinal side effects may limit tolerability in some patients. Indobufen presents a potential alternative, but its safety and efficacy need further validation. This study aimed to compare the efficacy and safety of indobufen versus aspirin in patients' post-CABG. This retrospective observational study included 39 patients who underwent CABG at two centers from January to December 2023. Patients were retrospectively assigned to two groups based on the antiplatelet therapy they received: the indobufen group (n = 19) and the aspirin group (n = 20). The primary endpoint was a composite of non-fatal myocardial infarction, stroke, and revascularization due to acute coronary syndrome in the intention-to-treat population. Postoperative data on platelet count, hemoglobin, D-dimer, activated partial thromboplastin time (APTT), and hospital stay length were collected. Transfusion rate, bleeding, thrombotic events, and gastrointestinal adverse reactions were compared between the two groups. Over the 8-to-18-month follow-up period, 5 patients (25%) in the aspirin group reached the primary endpoint, while none in the indobufen group did, a difference that was statistically significant (p = 0.02). Although the rates of non-fatal myocardial infarction, revascularization, stroke, and thrombotic events were higher in the aspirin group, these differences did not reach statistical significance. Importantly, the total bleeding events were markedly lower in the indobufen group (15.79% vs. 55%, p = 0.011), with major bleeding events also significantly reduced in the indobufen group (0% vs. 20%, p = 0.04). Both groups showed no significant differences were observed in postoperative hospital stay, hemoglobin, and D-dimer levels between the groups. However, the indobufen group demonstrated significantly lower platelet count and APTT. The average daily cost of indobufen was 27.8 times higher than that of aspirin. Indobufen demonstrates a comparable antiplatelet effect to aspirin and offers significant advantages in reducing gastrointestinal adverse reactions and bleeding risk. It can be considered a preferable alternative for patients who cannot tolerate or have contraindications to aspirin. Further large-scale clinical trials are needed to confirm its potential as the first-choice antiplatelet therapy post-CABG.

Healthcare service utilisation among adults with coronary artery disease in rural Aluva, South India: a community-based cross-sectional study

ObjectivesTo assess the pattern and determinants of healthcare service utilisation among adults with coronary artery disease (CAD) in a rural setting in Kerala, India.DesignA community-based cross-sectional analysis conducted within a...

Comparing E-Cigarettes and Traditional Cigarettes in Relation to Myocardial Infarction, Arrhythmias, and Sudden Cardiac Death: A Systematic Review and Meta-Analysis.

The use of electronic cigarettes (e-cigarettes) as a perceived safer alternative to traditional cigarettes has grown rapidly. However, the cardiovascular risks associated with e-cigarettes compared to regular cigarettes remain unclear. To systematically review and compare the cardiovascular outcomes of e-cigarette use versus traditional cigarette use, focusing on the risks of myocardial infarction, arrhythmias, and sudden death. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Peer-reviewed studies published in English were included if they reported cardiovascular outcomes related to e-cigarette or traditional cigarette use. A total of 20 studies were included, covering observational and interventional studies focusing on heart rate variability, myocardial infarction, arrhythmias, and sudden cardiac events. The quality of the evidence was assessed using the GRADE criteria, and data were extracted and analyzed based on the PICOS (Population, Interventions, Comparisons, Outcomes, and Study designs) framework. The systematic review found that both e-cigarettes and traditional cigarettes pose significant cardiovascular risks, with traditional cigarettes linked to a higher incidence of myocardial infarction, arrhythmias, and sudden cardiac death. E-cigarette users also face increased risks of arrhythmias and myocardial infarction compared to non-smokers, primarily due to the constituents of aerosolized e-liquid, including nicotine and flavorings, which contribute to adverse cardiac effects. Regular e-cigarette use, particularly in combination with traditional cigarette use, was associated with a heightened risk of myocardial infarction. Studies also reported heart function abnormalities, such as systolic and diastolic dysfunction, and reduced ejection fractions. Additionally, changes in heart rate variability, heart rate, and blood pressure were observed, indicating both acute and chronic effects of e-cigarettes on cardiovascular autonomic regulation. While e-cigarettes may present a lower cardiovascular risk compared to traditional cigarettes, they are not without harm. Both products are linked to increased risks of myocardial infarction and arrhythmias, though traditional cigarettes pose a higher overall threat. Given the limitations in the current evidence base, particularly concerning the long-term effects of e-cigarette use, further research is needed to clarify these cardiovascular risks and inform public health guidelines.

Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: A report from the GLORIA‐AF registry phase III

AbstractAimsAtrial fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations have not been fully elucidated, particularly with concomitant insulin use. This study aimed to analyse the associations between adverse events and DM, as well as adverse events and sole insulin use.Materials and MethodsOur analysis included individuals with AF from the prospective Global Registry on Long‐Term Oral Anti‐Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA‐AF) registry with 3‐year follow‐up. Outcomes included all‐cause death, major bleeding, cardiovascular (CV) death, myocardial infarction (MI), stroke, thromboembolism and major adverse cardiovascular events (MACE).ResultsA total of 15 861 AF individuals were included (age 70.0 ± 10.2 years; 55% male, 20% Asian), of whom, 3666 had DM (age 70.0 ± 9.5 years ; 59% male, 21% Asian). After adjustment, those with DM had higher risks of all‐cause death (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.28–1.66), CV death (HR: 1.53 95% CI: 1.27–1.86), major bleeding (HR: 1.23, 95% CI: 1.01–1.48), MI (HR: 1.50, 95% CI: 1.17–1.94) and MACE (HR: 1.42, 95% CI: 1.23–1.63). Compared to individuals with DM receiving oral hypoglycaemic agents, those receiving insulin alone were associated with increased risks of all‐cause death (HR: 2.16, 95% CI: 1.61–2.91), CV death (HR: 2.24, 95% CI: 1.45–3.47), major bleeding (HR: 1.89, 95% CI: 1. 21–2.95), MI (HR: 2.24, 95% CI: 1.31–3.82) and MACE (HR: 2.11, 95% CI: 1.54–2.88).ConclusionsDM was independently associated with higher risks of all‐cause death, CV death, MI, major bleeding and MACE in AF individuals. Individuals receiving insulin alone were associated with higher risks of all‐cause death, CV death, MI, major bleeding and MACE.

M2 Macrophage Exosomes Reverse Cardiac Functional Decline in Mice with Diet-Induced Myocardial Infarction by Suppressing Type 1 Interferon Signaling in Myeloid Cells.

Effective treatment strategies to alleviate heart failure that develops as a consequence of myocardial infarction (MI) remain an unmet need in cardiovascular medicine. In this study, we uncovered that exosomes produced by human THP-1 macrophages cultured with the cytokine IL-4 (THP1-IL4-exo), reverse cardiac functional decline in mice that develop MI as a consequence of diet-induced occlusive coronary atherosclerosis. Therapeutic benefits of THP1-IL4-exo stem from their ability to reprogram circulating Ly-6Chi monocytes into an M2-like phenotype and suppress Type 1 Interferon signaling in myeloid cells within the bone marrow, the circulation, and cardiac tissue. Collectively, these benefits suppress myelopoiesis, myeloid cell recruitment to cardiac tissue, and preserve populations of resident cardiac macrophages that together mitigate cardiac inflammation, adverse ventricular remodeling, and heart failure. Our findings introduce THP1-IL4-exo, one form of M2-macrophage exosomes, as novel therapeutics to preserve cardiac function subsequent to MI.

Serum Albumin-to-Creatinine Ratio Predicts One-Year Mortality in Elderly Patients with Non-ST-Elevation Acute Coronary Syndrome After Percutaneous Coronary Intervention: A Prospective Cohort Analysis.

BACKGROUND Recently, the albumin-to-creatinine ratio (ACR) has been suggested as a valuable biomarker for adverse events in acute myocardial infarction. However, the prognostic value of ACR in very elderly patients (≥80 years) with non-ST-elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI) remains unclear. MATERIAL AND METHODS A total of 354 very elderly patients with NSTE-ACS who underwent PCI were included in this study and followed up for 1 year. Patients were divided into 3 groups according to ACR tertiles. Logistic regression analysis proportional hazard model was used to determine the prognostic value of ACR. RESULTS Sixty-two patients (17.5%) with 114 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during 1-year follow-up. Patients with lower ACR tended to be older and had a lower serum albumin level and higher uric acid and creatinine levels (P<0.05). Moreover, patients with lower ACR levels had elevated all-cause mortality and MACCEs. Kaplan-Meier analysis suggested that patients with a lower ACR had a significantly lower survival rate free of all-cause mortality and MACCEs. Multivariable logistic regression analysis demonstrated that ACR was an independent predictor of all-cause mortality in these patients. ROC analysis showed that when ACR was ≤42.8, sensitivity and specificity were 75.2% and 80.2%, respectively, and the area under the ROC curve was 0.802 (95% CI: 0.745-0.859; P<0.001). CONCLUSIONS A lower ACR was associated with a higher incidence of all-cause mortality in very elderly patients with NSTE-ACS after PCI. The ACR is a promising indicator for risk stratification and prognostic assessment in these individuals.

Comparison of liberal versus restrictive transfusion strategies after hip surgery in patients with coronary artery disease: a post hoc analysis of the FOCUS trial

BackgroundThere are no clear recommendations for optimal transfusion thresholds for patients with coronary artery disease who undergo noncardiac surgery. By comparing restrictive and liberal transfusion strategies for coronary artery disease combined with hip surgery, this study hopes to provide recommendations for transfusion strategies in this special population.MethodsA total of 805 patients from the FOCUS trial (Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair) with coronary artery disease combined with hip surgery were divided into two groups based on transfusion thresholds: restricted transfusion (a hemoglobin level of 8 g/deciliter) and liberal transfusion (a hemoglobin threshold of 10 g/deciliter). The primary outcome of this study was a composite endpoint including in-hospital death, myocardial infarction, unstable angina, and acute heart failure. The secondary endpoints included other in-hospital adverse events and 30- and 60-day follow-up events. Analyses were performed by intention to treat.ResultsExcept for the proportion of congestive heart failure patients, the baseline levels of the two groups were comparable. The median number of transfusion units in the liberal transfusion group was 2 units, and the median transfusion volume in the restricted transfusion group was 0 units. The primary outcome was not significantly different between the two groups (9.2% vs. 9.4%, p = 0.91). The incidence of in-hospital myocardial infarction events was lower in the liberal transfusion group than in the restricted transfusion group (3.2% vs. 6.2%) (OR = 0.51, P = 0.048). The remaining in-hospital endpoint events, except for myocardial infarction, were not significantly different between the two groups. The 30-day and 60-day endpoints of death and inability to walk independently were not significantly different between the two groups, with ORs (95% CI) of 1.00 (0.75–1.31) and 1.06 (0.80–1.41), respectively. We also found no interaction between transfusion strategies and factors such as age, sex, or multiple underlying comorbidities at the 60-day follow-up.ConclusionsThere was no significant difference in the in-hospital, 30-day or 60-day outcome endpoints between the two groups. However, this study demonstrated that a liberal transfusion strategy tends to reduce the incidence of in-hospital myocardial infarction events in patients with coronary artery disease combined with hip surgery compared to a restrictive transfusion strategy. More high-quality studies should be designed to investigate the optimal transfusion threshold in patients with coronary artery disease treated without cardiac surgery.