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Experimental evidence suggests that cyclosporine may attenuate myocardial reperfusion injury. In a pilot trial, 58 patients with acute ST-elevation myocardial infarction were randomly assigned to receive an intravenous bolus of either cyclosporine or saline immediately before undergoing percutaneous coronary intervention. Creatine kinase release was significantly reduced in the patients who received cyclosporine. These results require confirmation in a larger trial. Experimental evidence suggests that cyclosporine may attenuate myocardial reperfusion injury. In a pilot trial, creatine kinase release was significantly reduced in the patients who received cyclosporine. Myocardial infarction is a disabling disease that is common in the United States, with more than 1.5 million new cases diagnosed each year. 1 , 2 Infarct size is a major determinant of mortality in myocardial infarction. 3 , 4 Limitation of infarct size has therefore been an important objective of strategies to improve outcomes. Currently, the most effective way to limit infarct size is to reperfuse the jeopardized myocardium as soon as possible with the use of coronary angioplasty or thrombolysis and to prevent reocclusion of the coronary artery with the use of antiplatelet therapy. Although reperfusion is undoubtedly beneficial, it has detrimental . . .

BackgroundSoluble form suppression of tumorigenicity 2 (sST2) is known to have prognostic value in ST-elevation myocardial infarction (STEMI) and could impact mortality after acute ischemic stroke (AIS). However, before considering sST2 as a therapeutic target, the kinetics of release and its association with adverse clinical events in both STEMI and AIS patients have to be determined.MethodsWe prospectively enrolled 251 STEMI patients, treated with primary percutaneous coronary intervention, and 152 AIS patients treated with mechanical thrombectomy. We evaluated the level of sST2 in patient sera at five time point (admission, 4, 24, 48 h and 1 month from admission for STEMI patients and admission, 6, 24, 48 h and 3 months from admission for AIS patients). Major adverse clinical events (MACE) (all-cause death, acute myocardial infarction, stroke or hospitalization for heart failure) in STEMI patients and all-cause death in AIS patients were recorded during a 12-month follow-up.ResultsMean age of the study population was 59 ± 12 and 69 ± 15 years in STEMI and AIS patients, respectively. In STEMI patients, sST2 peaked 24 h after admission (25.5 ng/mL interquartile range (IQR) [14.9–29.1]) whereas an earlier and lower peak was observed in AIS patients (16.8 ng/mL IQR [15.2–18.3] at 6 h). Twenty-five (10.0%) STEMI patients experienced a MACE and 12 (7.9%) AIS patients had all-cause death within the first 12 months. A high level of sST2 at 24 h was associated with MACE in STEMI patients (hazard ratio (HR) = 2.5; 95% confidence interval (CI) [1.1–5.6], p = 0.03) and all-cause death in AIS patients (HR = 11.7; 95% CI [3.8–36.2], p < 0.01) within the first 12 months.ConclusionsThe study highlights that sST2 levels at 24 h are associated with an increased risk to adverse clinical events in both diseases.

Incidence and mortality rates for cardiovascular disease are declining, but it still remains a major cause of morbidity and mortality. Drug treatments to slow the progression of atherosclerosis focus on reducing cholesterol levels. The paradigm shift to consider atherosclerosis an inflammatory disease by itself has led to the development of new treatments. In this article, we discuss the pathophysiology of inflammation and focus attention on therapeutics targeting different inflammatory pathways of atherosclerosis and myocardial infarction. In atherosclerosis, colchicine is included in new recommendations, and eight randomized clinical trials are testing new drugs in different inflammatory pathways. After a myocardial infarction, no drug has shown a significant benefit, but we present four randomized clinical trials with new treatments targeting inflammation.

BackgroundAging is a risk factor for type 2 myocardial infarction or myocardial injury, but few data are available on the elderly. We aimed to determine the factors associated with these pathologies and mortality in the elderly population and its age classes.MethodsA retrospective cohort of all patients with oxygen mismatch (anemia, hypoxia, tachycardia, hypo/hypertension) for whom a troponin drawn was performed at admission in 2 emergency departments. Medical records were reviewed and classified as having type 2 myocardial infarction, acute or chronic myocardial injury, or no myocardial injury.ResultsOf the 824 patients who presented with oxygen mismatch, 675 (81.9%) were older than 65 years. Age over 85 years was a risk factor for acute non-ischemic myocardial injury (odds ratio, 95% confidence interval 2.23, 1.34–3.73). Non-ischemic myocardial injury was associated with hypoxemia, tachycardia, and acute renal failure in those older than 85 years, but only with acute infection in the 75–84-year-old group. Type 2 myocardial infarction was associated only with acute renal failure in the oldest group and, in the 75–84-year-old group, with acute heart failure and shock. Patients older than 85 years with acute myocardial injury, with or without infarction, had a higher in-hospital mortality, but subsequently, mortality depends more on the comorbidities than on age.ConclusionFactors associated with type 2 myocardial infarction and acute non-ischemic myocardial injury in elderly admitted with oxygen mismatch vary notably between age classes. They are associated with in-hospital mortality but not with subsequent mortality when other cormorbities are taken into account.

ObjectiveIn the COVERT-MI randomised placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days in acute ST-elevated myocardial infarction did not reduce infarct size but was associated with a significant increase in left ventricular thrombus (LVT) in comparison to placebo. We aimed to assess the 1-year clinical outcomes of the study population.MethodsThis study is a follow-up analysis of the COVERT-MI study on prespecified secondary clinical endpoints at 1 year. The primary endpoint of this study was a composite of major adverse cardiovascular events (MACEs), including all-cause death, acute coronary syndromes, heart failure events, ischaemic strokes, sustained ventricular arrhythmias and acute kidney injury at 1-year follow-up. The quality of life (QOL) and the drug therapy prescription were also assessed.ResultsAt 1 year, 192 patients (101 patients in the colchicine group, 91 in the placebo group) were followed up. Seventy-six (39.6%) MACEs were reported in the study population. There was no significant difference regarding the number of MACEs between groups: 36 (35.6%) in the colchicine group and 40 (44.1%) in the placebo group (p=0.3). There were no differences in the occurrence of ischaemic strokes between the colchicine group and the control group (3 (3%) vs 2 (2.2%), respectively, p=0.99). There was a trend towards fewer heart failure events in the colchicine group compared with the placebo group (12 (11.9%) vs 18 (19.8%), p=0.20). There was no significant difference in QOL scores at 1 year (75.8±15.7 vs 72.7±16.2 respectively, p=0.18).ConclusionsThere was no significant difference between the colchicine and placebo groups at 1 year regarding MACEs, especially concerning deaths or ischaemic strokes. No excess of ischaemic adverse events was observed despite the initial increase in LVT in the colchicine group.Trial registration numberNCT0315681.

Background: Vasoplegic syndrome after orthotopic heart transplantation (OHT) or left ventricular assist device (LVAD) implantation is a rare but highly lethal syndrome with complex etiologies. The objective of this study was to assess if the preoperative use of sacubitril-valsartan combination is associated with an increased vasoplegic syndrome (VS) frequency after OHT or LVAD implantation and its relationship with 30-day mortality. Methods: A retrospective review of perioperative data, between January 2016 and December 2017, from 73 consecutive OHT and LVAD surgery adult patients at our institution was performed. VS was defined as normal cardiac output with persistent low systemic resistance requiring a norepinephrine intravenous perfusion > 0.5 µg/kg/min and the absence of sepsis or hemorrhagic shock within 48 h after surgery. Patients were all followed-up for adverse events and all-cause mortality at 30 days. Results: In our cohort of 73 patients (median age 51.7 years, 65% male patients), 25 (34%) patients developed VS. Twenty-two (30.1%) patients were on ARNI at the time of surgery, 31 (42.5%) were on other RAS blockers, 12 (16.4%) were on norepinephrine and 8 (11%) had no pre-operative drug. The pre-operative use of any vasoactive agent, was not significantly associated with VS (OR = 1.36; IC95% [0.78; 2.35]; p = 0.38). The pre-operative use of an ARNI compared to all other groups was not significantly associated with VS (OR = 2.0; IC95% [0.71; 5.62]; p = 0.19). The pre-operative use of an ARNI compared to other RAS blockers was also not significantly associated with VS (OR = 1.25; IC95% [0.37; 4.26]; p = 0.72). At 30 days, 18 (24.7%) patients had died. The pre-operative treatment with ARNI, or other RAS inhibitors was associated with a significantly lower rate of death compared to the absence of treatment (HR = 0.11; IC95% [0.02; 0.55]; p = 0.009 for ARNI and HR = 0.20; IC95% [0.06; 0.69]; p = 0.011 for other RASi). Conclusions: Preoperative use of sacubitril-valsartan was not significantly associated with development of vasoplegic syndrome in patients undergoing OHT or LVAD surgery. Furthermore, our data suggests a significant 30-day survival benefit with efficient renin-angiotensin blockade before surgery.

ObjectivesRegional differences in heart failure with preserved ejection fraction (HFpEF) care have been reported. We aimed to assess a physician-reported HFpEF management in the Russian Federation (RF) and a variation in the diagnosis and treatment of HFpEF between the RF and the European Union (EU).Design/settingsIt is a post hoc analysis of an academic web-based international HFpEF designed as a cross-sectional survey and conducted between May 2023 and July 2023.ParticipantsMedical doctors who work in the fields of cardiology and general medicine.ResultsAmong 1460 medical doctors who completed the study were 166 Russian and 646 European specialists. The responders were comparable across the groups in most of the baseline characteristics, except that RF specialists were less likely to be heart failure specialists (RF: 2% vs EU: 26%) and less often worked in academic environments (RF: 17% vs EU: 61%). The utilisation of specific echocardiography parameters (RF: 66% vs EU: 80%) and natriuretic peptides (RF: 83% vs EU: 91%) to establish a diagnosis of HFpEF was less frequent in RF compared with EU, while HFpEF scores were more likely to be used by Russian physicians (RF: 58% vs EU: 40%). In the settings when all HF medications are available, responders of both regions prioritised sodium-glucose co-transporter type 2 inhibitors (SGLT2is) (mean rank: RF: 2.6 (IQR: 2.3–3) vs EU: 2.3 (IQR: 2.2–2.5)), followed by diuretics in the EU and ACE inhibitors in the RF. Every second responder in both regions preferred SGLT-2is if only one drug was available (RF: 57% vs EU 51%).ConclusionsThe results reveal discrepancies in physician-reported HFpEF management between RF and EU responders, particularly in the diagnostic workup. Although the utilisation of relevant diagnostic tests was lower in the RF compared with the EU, these were used by two-thirds of Russian respondents. Nevertheless, further measures are required to improve the care of HFpEF patients in the RF.

Background Although diabetes mellitus (DM) and insulin resistance associate with adverse cardiac events, the associations of left ventricular (LV) remodeling and function with compromised glucose metabolism have not been fully evaluated in a general population. We used cardiovascular magnetic resonance (CMR) to evaluate how CMR indices are associated with DM or insulin resistance among participants before developing cardiac events. Methods We studied 1476 participants who were free of clinical cardiovascular disease and who underwent tagged CMR in the Multi-Ethnic Study of Atherosclerosis (MESA). LV shape and longitudinal myocardial shortening and torsion were assessed by CMR. A higher sphericity index represents a more spherical LV shape. Multivariable linear regression was used to evaluate the associations of DM or homeostasis model assessment-estimated insulin resistance (HOMA-IR) with CMR indices. Results In multiple linear regression, longitudinal shortening was lower in impaired fasting glucose than normal fasting glucose (NFG) (0.36% lower vs. NFG, p  < 0.05); torsion was greater in treated DM (0.24 °/cm greater vs. NFG, p  < 0.05) after full adjustments. Among participants without DM, greater log-HOMA-IR was correlated with greater LV mass (3.92 g/index, p  < 0.05) and LV mass-to-volume ratio (0.05 /index, p  < 0.01), and lower sphericity index (− 1.26/index, p  < 0.01). Greater log-HOMA IR was associated with lower longitudinal shortening (− 0.26%/index, p  < 0.05) and circumferential shortening (− 0.30%/index, p < 0.05). Torsion was positively correlated with log-HOMA-IR until 1.5 of log-HOMA-IR (0.16 °/cm/index, p  = 0.030).), and tended to fall once above 1.5 of log-HOMA-IR (− 0.50 °/cm/index, p  = 0.203). The sphericity index was associated negatively with LV mass-to-volume ratio (− 0.02/%, p  < 0.001) and torsion (− 0.03°/cm/%, p  < 0.001). Conclusions Glucose metabolism disorders are associated with LV concentric remodeling, less spherical shape, and reduced systolic myocardial shortening in the general population. Although torsion is higher in participants who are treated for DM and impaired insulin resistance, myocardial shortening was progressively decreased with higher HOMA-IR and torsion was increased only with less severe insulin resistance. Clinical trial registration Multi-Ethnic Study of Atherosclerosis (MESA): A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org/ . Study Start Date: January 1999 ( NCT00005487 ).

Background The aim of this study was to estimate the mean cost per caregiver of informal care during the first year after myocardial infarction event in France. Methods We used the Handicap-Santé French survey carried out in 2008 to obtain data about MI survivors and their caregivers. After obtaining the total number of informal care hours provided by caregiver during the first year after MI event, we estimated the value of informal care using the proxy good method and the contingent valuation method. Results For MI people receiving informal care, an annual mean cost was estimated at €12,404 (SD = 13,012) with the proxy good method and €12,798 (SD = 13,425) with the contingent valuation method per caregiver during the first year after myocardial infarction event. Conclusions The present study suggests that informal care should be included more widely in economic evaluations in order not to underestimate the cost of diseases which induce disability.

Abstract Aims Diagnosing acute heart failure (AHF) remains particularly challenging in older patients. Natriuretic peptides are recommended as valuable diagnostic tools in this context. This study aims to establish the diagnostic thresholds of B‐type natriuretic peptide (BNP) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) for AHF in patients aged over 75 years, both with and without co‐morbidities. Methods and results In this retrospective longitudinal multicentre cohort study, data were gathered from 12 071 hospitalized patients aged 75 years or older, presenting with acute dyspnoea and undergoing BNP or NT‐proBNP measurement within 48 h of admission across 10 Assistance Publique‐Hôpitaux de Paris facilities between 2011 and 2022, encompassing geriatrics, cardiology, and pulmonology departments. Final diagnoses were categorized using ICD‐10 criteria as either AHF or other acute respiratory conditions such as COPD exacerbation, pulmonary embolism, and pneumonia. The mean (SD) age of the population was 84.0 (80.0, 89.0) years, with 52.7% being female. Out of these, 7946 (65.8%) were diagnosed with AHF upon discharge. For NT‐proBNP, the identified ‘optimal’ threshold for diagnosing AHF was 1748 ng/L, with a positive predictive value (PPV) of 84%. Among patients aged over 85 years, a threshold of 2235 pg/mL for NT‐proBNP was associated with an 84% PPV. In patients with atrial fibrillation (AF), a threshold of 2332 pg/mL for NT‐proBNP demonstrated a PPV of 90% for AHF diagnosis. Additionally, in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min, a threshold of 3474 pg/mL for NT‐proBNP yielded a 90% PPV for AHF diagnosis. In male patients, a threshold of 1800 pg/mL showed an 85% PPV for AHF diagnosis, while in patients with obesity, a threshold of 1375 pg/mL demonstrated an 85% PPV for AHF diagnosis. Conclusions In older patients, we found significant effects of co‐morbidities on natriuretic peptides results, particularly in patients over 85 years old, older patients with abnormal renal function, obesity, and atrial fibrillation. Despite the consideration of those co‐morbid conditions, NT‐proBNP and BNP level continue to demonstrate utility in the diagnosis of AHF in older patients.