Aims Identification and management of the Standard Modifiable Cardiovascular Risk Factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes and smoking) has substantially improved cardiovascular ...disease outcomes. However, cardiovascular disease remains the leading cause of death worldwide. Suspecting an evolving pattern of risk factor profiles in the ST elevation myocardial infarction (STEMI) population with the improvements in primary care, we hypothesized that the proportion of 'SMuRFless' STEMI patients may have increased. Methods/results We performed a single centre retrospective study of consecutive STEMI patients presenting from January 2006 to December 2014. Over the study period 132/695 (25%) STEMI patients had 0 SMuRFs, a proportion that did not significantly change with age, gender or family history. The proportion of STEMI patients who were SMuRFless in 2006 was 11%, which increased to 27% by 2014 (odds ratio 1.12 per year, 95% confidence interval: 1.04-1.22). The proportion of patients with hypercholesterolaemia decreased (odds ratio 0.92, 95% confidence interval 0.86-0.98), as did the proportion of current smokers (odds ratio 0.93, 95% confidence interval 0.86-0.99), with no significant change in the proportion of patients with diabetes and hypertension. SMuRF status was not associated with extent of coronary disease; in-hospital outcomes, or discharge prescribing patterns. Conclusion The proportion of STEMI patients with STEMI poorly explained by SMuRFs is high, and is significantly increasing. This highlights the need for bold approaches to discover new mechanisms and markers for early identification of these patients, as well as to understand the outcomes and develop new targeted therapies.
Human induced pluripotent stem cells with normal (wild-type) or upregulated (overexpressed) levels of CCND2 (cyclin D2) expression were differentiated into cardiomyocytes (CCND2
CMs or CCND2
CMs, ...respectively) and injected into infarcted pig hearts.
Acute myocardial infarction was induced by a 60-minute occlusion of the left anterior descending coronary artery. Immediately after reperfusion, CCND2
CMs or CCND2
CMs (3×10
cells each) or an equivalent volume of the delivery vehicle was injected around the infarct border zone area.
The number of the engrafted CCND2
CMs exceeded that of the engrafted CCND2
CMs from 6- to 8-fold, rising from 1 week to 4 weeks after implantation. In contrast to the treatment with the CCND2
CMs or the delivery vehicle, the administration of CCND2
CM was associated with significantly improved left ventricular function, as revealed by magnetic resonance imaging. This correlated with reduction of infarct size, fibrosis, ventricular hypertrophy, and cardiomyocyte apoptosis, and increase of vascular density and arterial density, as per histologic analysis of the treated hearts. Expression of cell proliferation markers (eg, Ki67, phosphorylated histone 3, and Aurora B kinase) was also significantly upregulated in the recipient cardiomyocytes from the CCND2
CM-treated than from the CCND2
CM-treated pigs. The cell proliferation rate and the hypoxia tolerance measured in cultured human induced pluripotent stem cell cardiomyocytes were significantly greater after treatment with exosomes isolated from the CCND2
CMs (CCND2
Exos) than from the CCND2
CMs (CCND2
Exos). As demonstrated by our study, CCND2
Exos can also promote the proliferation activity of postnatal rat and adult mouse cardiomyocytes. A bulk miRNA sequencing analysis of CCND2
Exos versus CCND2
Exos identified 206 and 91 miRNAs that were significantly upregulated and downregulated, respectively. Gene ontology enrichment analysis identified significant differences in the expression profiles of miRNAs from various functional categories and pathways, including miRNAs implicated in cell-cycle checkpoints (G2/M and G1/S transitions), or the mechanism of cytokinesis.
We demonstrated that enhanced potency of CCND2
CMs promoted myocyte proliferation in both grafts and recipient tissue in a large mammal acute myocardial infarction model. These results suggest that CCND2
CMs transplantation may be a potential therapeutic strategy for the repair of infarcted hearts.
REDUCE-IT was a double-blind trial that randomized 8,179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides to icosapent ethyl (IPE) or ...placebo. There was a significant reduction in the primary endpoint, including death from cardiovascular (CV) causes. The specific impact of IPE among patients with prior myocardial infarction (MI) was unknown.
Our goal was to examine the benefit of IPE on ischemic events among patients with prior MI in REDUCE-IT.
We performed post hoc analyses of patients with prior MI. The primary endpoint was CV death, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary endpoint was CV death, MI, or stroke.
A total of 3,693 patients had a history of prior MI. The primary endpoint was reduced from 26.1% to 20.2% with IPE vs placebo; HR: 0.74 (95% CI: 0.65-0.85; P = 0.00001). The key secondary endpoint was reduced from 18.0% to 13.3%; HR: 0.71 (95% CI: 0.61-0.84; P = 0.00006). There was also a significant 35% relative risk reduction in total ischemic events (P = 0.0000001), a 34% reduction in MI (P = 0.00009), a 30% reduction in CV death (P = 0.01), and a 20% lower rate of all-cause mortality (P = 0.054), although there was a slight increase in atrial fibrillation. Sudden cardiac death and cardiac arrest were also significantly reduced by 40% and 56%, respectively.
Patients with a history of prior MI in REDUCE-IT treated with IPE demonstrated large and significant relative and absolute risk reductions in ischemic events, including CV death. (A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High Risk Patients With Hypertriglyceridemia and on Statin. The Primary Objective is to Evaluate the Effect of 4 g/Day AMR101 for Preventing the Occurrence of a First Major Cardiovascular Event. REDUCE-IT; NCT01492361)
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Myocardial bridge (MB) often an inoffensive condition that goes in one or more of the coronary arteries through the heart muscle instead of lying on its surface. MBs sometimes leads to myocardial ...ischemic symptoms such as chest pain, even an occurrence of myocardial infarction. However, reports of severe and recurrent cardiac adverse events related to the MBs are rare.
A 44-year-old male patient who suffered from a four-hour crushing chest pain ten years ago, was diagnosed as acute anterior ST-elevation myocardial infarction (STEMI). The initial findings of coronary angiography (CAG) showed MB was located in the middle part of the left anterior descending coronary artery (LAD). The patient was managed medically. Another re-attack of similar previous chest pain characteristics occured just after 3 days of discharge. Supra-arterial myotomy and CABG were the next adopted management. Postoperative progression was uneventful. However, 32 months after surgical treatment, the patient experienced an abrupt onset of chest pain accompanied by loss of consciousness. The ECG showed ventricular fibrillation (VF). After electrical cardioversion, an immediate CAG followed by CTA was performed which excluded thrombus or acute occlusion in the native coronary artery and an occlusion was observed at the end of the left internal mammary artery. An implantable cardioverter-defibrillator (ICD) was successfully performed for prevention of malignant arrhythmia. During ten years of follow-up, no complications have been identified.
Although MB is mostly benign, it may lead to significant cardiovascular consequences. Supra-arterial myotomy is an appropriate treatment option for this patient who failed to optimal medical therapy. Furthermore, ICD implantation must be considered in order to prevent malignant ventricular arrhythmia caused by continuous spasm resulting in ischemia. Further investigations are required to confirm the clinical effectiveness of these procedures.
Background
Several biomarkers have individually been shown to be useful for risk stratification in patients with acute myocardial infarction (MI). The optimal multimarker strategy remains undefined.
...Methods and Results
Biomarkers representing different pathobiological axes were studied, including myocardial stress/structural changes (NT‐pro B‐type natriuretic peptide NT‐proBNP, midregional proatrial natriuretic peptide MR‐proANP, suppression of tumorigenicity 2 ST2, galectin‐3, midregional proadrenomedullin MR‐proADM, and copeptin), myonecrosis (troponin T), and inflammation (myeloperoxidase MPO, high sensitivity C‐reactive protein hsCRP, pregnancy‐associated plasma protein A PAPP‐A, and growth‐differentiation factor‐15 GDF‐15), in up to 1258 patients from Clopidogrel as Adjunctive Reperfusion Therapy‐Thrombolysis in Myocardial Infarction 28 (CLARITY‐TIMI 28), a randomized trial of clopidogrel in ST‐elevation MI (STEMI). Patients were followed for 30 days. Biomarker analyses were adjusted for traditional clinical variables. Forward step‐wise selection was used to assess a multimarker strategy. After adjustment for clinical variables and using a dichotomous cutpoint, 7 biomarkers were each significantly associated with a higher odds of cardiovascular death or heart failure (HF) through 30 days, including NT‐proBNP (adjusted odds ratio ORadj, 2.54; 95% CI, 1.47–4.37), MR‐proANP (2.18; 1.27–3.76), ST2 (2.88; 1.72–4.81), troponin T (4.13; 1.85–9.20), MPO (2.75; 1.20–6.27), hsCRP (1.96, 1.17–3.30), and PAPP‐A (3.04; 1.17–7.88). In a multimarker model, 3 biomarkers emerged as significant and complementary predictors of cardiovascular death or HF: ST2 (ORadj, 2.87; 1.61–5.12), troponin T (2.34; 1.09–5.01 and 4.13, 1.85–9.20, respectively for intermediate and high levels), and MPO (2.49; 1.04–5.96). When added to the TIMI STEMI Risk Score alone, the multimarker risk score significantly improved the C‐statistic (area under the curve, 0.75 95% CI, 0.69–0.81 to 0.82 0.78–0.87; P=0.001), net reclassification index (0.93; P<0.001), and integrated discrimination index (0.09; P<0.001).
Conclusions
In patients with STEMI, a multimarker strategy that combines biomarkers across pathobiological axes of myocardial stress, myocyte necrosis, and inflammation provides incremental prognostic information for prediction of cardiovascular death or HF.
The COVID-19 pandemic has had diverse effects on population health and psychology in relation to non-COVID-19 diseases, as well as on COVID-19 infection. Fewer patients with acute myocardial ...infarction (AMI) sought medical attention during the first lockdown of the pandemic.
We conducted a retrospective cohort study of Clalit Health Services patients treated in multiple hospitals for AMI. We examined the numbers and characteristics of the patients and 30-day mortality during three 5-week phases of the first wave of the COVID-19 pandemic in Israel: pre-lockdown (N = 702), lockdown (N = 584), and lockdown-lift (N = 669). We compared data for the same period in 2018 and 2019. We stratified the data by ST-elevation myocardial infarction (STEMI) and non-STEMI. AMI hospitalizations during the lockdown were 17% lower than in the pre-lockdown period (rate ratio-0.83, 95% CI 0.74–0.93), and 22% and 31% lower than in the corresponding periods in 2018 and 2019, respectively. The reduction was mainly attributed to non-STEMI hospitalizations (26% lower than the pre-lockdown period in 2020). Hospitalizations due to both STEMI and non-STEMI were moderately reduced during the post-lockdown period compared to the corresponding periods in 2018 and 2019. Thirty-day mortality rate was similar for all the periods assessed.
The number of hospitalized patients with AMI during the first COVID-19 lockdown and post-lockdown periods was significantly reduced, without significant changes in 30-day mortality rates.
•Acute myocardial infarction (MI) hospitalization rates during the COVID-19 lockdown were studied•Hospitalization rates were lower during lockdown than in the pre-lockdown period and in the equivalent periods in 2018-9•The reduction was mainly attributed to non-STEMI hospitalizations•Thirty-day mortality rate was similar for all the periods assessed
Although in situ restoration of blood supply to the infarction region and attenuating pre‐existing extracellular matrix degradation remain potential therapeutic approaches for myocardial infarction ...(MI), local delivery of therapeutics has been limited by low accumulation (inefficacy) and unnecessary diffusion (toxicity). Here, a dual functional MI‐responsive hydrogel is fabricated for on‐demand drug delivery to promote angiogenesis and inhibit cardiac remodeling by targeting upregulated matrix metalloproteinase‐2/9 (MMP‐2/9) after MI. A glutathione (GSH)‐modified collagen hydrogel (collagen‐GSH) is prepared by conjugating collagen amine groups with GSH sulfhydryl groups and the recombinant protein GST‐TIMP‐bFGF (bFGF: basic fibroblast growth factor) by fusing bFGF with glutathione‐S‐transferase (GST) and MMP‐2/9 cleavable peptide PLGLAG (TIMP). Specific binding between GST and GSH significantly improves the amount of GST‐TIMP‐bFGF loaded in collagen‐GSH hydrogel. The TIMP peptide enclosed between GST and bFGF responds to MMPs for on‐demand release during MI. Additionally, the TIMP peptide is a competitive substrate of MMPs that inhibits the excessive degradation of cardiac matrix by MMPs after MI. GST‐TIMP‐bFGF/collagen‐GSH hydrogels promote the recovery of MI rats by enhancing vascularization and ameliorating myocardium remodeling. The results suggest that on‐demand growth factor delivery by synchronously controlling binding and responsive release to promote angiogenesis and attenuate cardiac remodeling might be promising for the treatment of ischemic heart disease.
A matrix metalloproteinase (MMP)‐responsive hydrogel is designed to achieve on‐demand basic fibroblast growth factor release at the site of a myocardial infarct for increasing the local protein concentration and reducing unnecessary diffusion, and competitive inhibition of MMP enzymatic activity for reducing adverse myocardial remodeling. Myocardial injection of the MMP‐responsive hydrogel results in significantly improved cardiac function, increased vascularization, and ameliorated cardiac remodeling, with good clinical application prospects.
The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric ...acid (SUA) in predicting fatal myocardial infaction (MI) in women and men.
The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months.
A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P < 0.01), but not in men.
The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.
The objective of the study was to identify any changes in primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in England by analysing procedural numbers, ...clinical characteristics and patient outcomes during the COVID-19 pandemic.
We conducted a retrospective cohort study of patients who underwent PCI in England between January 2017 and April 2020 in the British Cardiovascular Intervention Society-National Institute of Cardiovascular Outcomes Research database. Analysis was restricted to 44 hospitals that reported contemporaneous activity on PCI. Only patients with primary PCI for STEMI were included in the analysis.
A total of 34 127 patients with STEMI (primary PCI 33 938, facilitated PCI 108, rescue PCI 81) were included in the study. There was a decline in the number of procedures by 43% (n=497) in April 2020 compared with the average monthly procedures between 2017 and 2019 (n=865). For all patients, the median time from symptom to hospital showed increased after the lockdown (150 (99-270) vs 135 (89-250) min, p=0.004) and a longer door-to-balloon time after the lockdown (48 (21-112) vs 37 (16-94) min, p<0.001). The in-hospital mortality rate was 4.8% before the lockdown and 3.5% after the lockdown (p=0.12). Following adjustment for baseline characteristics, no differences were observed for in-hospital death (OR 0.87, 95% CI 0.45 to 1.68, p=0.67) and major adverse cardiovascular events (OR 0.71, 95% CI 0.39 to 1.32, p=0.28).
Following the lockdown in England, we observed a decline in primary PCI procedures for STEMI and increases in overall symptom-to-hospital and door-to-balloon time for patients with STEMI. Restructuring health services during COVID-19 has not adversely influenced in-hospital outcomes.
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