Natural History of Myocardial αvß3 Integrin Expression After Acute Myocardial Infarction: Correlation with Changes in Myocardial Blood Flow.

Angiogenesis is an essential part of the cardiac repair process after myocardial infarction, but its spatiotemporal dynamics remain to be fully deciphered.68Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting αvß3 integrin expression, which is a marker of angiogenesis. Methods: In this prospective single-center trial, we aimed to monitor angiogenesis through myocardial integrin αvß3 expression in 20 patients with ST-segment elevation myocardial infarction (STEMI). In addition, the correlations between the expression levels of myocardial αvß3 integrin and the subsequent changes in 82Rb PET/CT parameters, including rest and stress myocardial blood flow (MBF), myocardial flow reserve (MFR), and wall motion abnormalities, were assessed. The patients underwent 68Ga-NODAGA-RGD PET/CT and rest and stress 82Rb-PET/CT at 1 wk, 1 mo, and 3 mo after STEMI. To assess 68Ga-NODAGA-RGD uptake, the summed rest 82Rb and 68Ga-NODAGA-RGD images were coregistered, and segmental SUVs were calculated (RGD SUV). Results: At 1 wk after STEMI, 19 participants (95%) presented increased 68Ga-NODAGA-RGD uptake in the infarcted myocardium. Seventeen participants completed the full imaging series. The values of the RGD SUV in the infarcted myocardium were stable 1 mo after STEMI (1 wk vs. 1 mo, 1.47 g/mL [interquartile range (IQR), 1.37-1.64 g/mL] vs. 1.47 g/mL [IQR, 1.30-1.66 g/mL]; P = 0.9), followed by a significant partial decrease at 3 mo (1.32 g/mL [IQR, 1.12-1.71 g/mL]; P = 0.011 vs. 1 wk and 0.018 vs. 1 mo). In segment-based analysis, positive correlations were found between RGD SUV at 1 wk and the subsequent changes in stress MBF (Spearman ρ: r = 0.17, P = 0.0033) and MFR (Spearman ρ: r = 0.31, P < 0.0001) at 1 mo. A negative correlation was found between RGD SUV at 1 wk and the subsequent changes in wall motion abnormalities at 3 mo (Spearman ρ: r = -0.12, P = 0.035). Conclusion: The present study found that αvß3 integrin expression is significantly increased in the infarcted myocardium 1 wk after STEMI. This expression remains stable after 1 mo and partially decreases after 3 mo. Initial αvß3 integrin expression at 1 wk is significantly weakly correlated with subsequent improvements in stress MBF, MFR, and wall motion analysis.

Oxidation-reduction imaging of myoglobin reveals two-phase oxidation in the reperfused myocardium.

Myocardial infarction (MI) is a serious acute cardiovascular syndrome that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic-reperfusion settings, a burst of reactive oxygen species is generated, leading to redox imbalance that could be attributed to several molecules, including myoglobin. Myoglobin is dynamic and exhibits various oxidation-reduction states that have been an early subject of attention in the food industry, specifically for meat consumers. However, rarely if ever have the myoglobin optical properties been used to measure the severity of MI. In the current study, we develop a novel imaging pipeline that integrates tissue clearing, confocal and light sheet fluorescence microscopy, combined with imaging analysis, and processing tools to investigate and characterize the oxidation-reduction states of myoglobin in the ischemic area of the cleared myocardium post-MI. Using spectral imaging, we have characterized the endogenous fluorescence of the myocardium and demonstrated that it is partly composed by fluorescence of myoglobin. Under ischemia-reperfusion experimental settings, we report that the infarcted myocardium spectral signature is similar to that of oxidized myoglobin signal that peaks 3 h post-reperfusion and decreases with cardioprotection. The infarct size assessed by oxidation-reduction imaging at 3 h post-reperfusion was correlated to the one estimated with late gadolinium enhancement MRI at 24 h post-reperfusion. In conclusion, this original work suggests that the redox state of myoglobin can be used as a promising imaging biomarker for characterizing and estimating the size of the MI during early phases of reperfusion.

[Natriuretic peptides in the diagnosis and monitoring of heart failure]. / Peptides natriurétiques dans le diagnostic et le suivi de l'insuffisance cardiaque.

NATRIURETIC PEPTIDES IN THE DIAGNOSIS AND MONITORING OF CARDIAC FAILURE. Heart failure (HF) is a serious and common disease requiring a prompt diagnosis for appropriate management. Natriuretic peptides, such as BNP and NT-proBNP, play a crucial role in diagnosing HF due to their s pecificity and reproducibility. It is important to measuring natriuretic peptides, especially in cases of acute dyspnea, to differentiate cardiac causes from others. Specific thresholds are recommended, with high values strongly suggest HF, while normal levels rule out the diagnosis. Clinical characteristics, such as age, renal function, atrial fibrillation, obesity, and gender, influence natriuretic peptides levels and should be considered in interpretation. For diabetic, hypertensive, and obese patients, early screening for HF through natriuretic peptides measurement is crucial. Furthermore, these natriuretic peptides are useful for monitoring chronic heart failure patients. They assist in confirming decompensation, titrating treatment, evaluating treatment response, and establishing prognosis. However, it's essential to choose a single biomarker (BNP or NT-proBNP) to avoid confusion.

DANS LE DIAGNOSTIC ET LE SUIVI DE L'INSUFFISANCE CARDIAQUE. L'insuffisance cardiaque (IC) est une maladie grave et fréquente nécessitant un diagnostic rapide pour une prise en charge adéquate. Les peptides natriurétiques, tels que le BNP et le NT-proBNP, jouent un rôle essentiel dans le diagnostic de l'IC en raison de leur spécificité et de leur reproductibilité. Il est important de doser les peptides natriurétiques, en particulier lors d'une dyspnée aiguë, pour différencier les causes cardiaques des autres. Des seuils spécifiques sont recommandés, et des valeurs élevées évoquent fortement une IC, tandis que des taux normaux écartent le diagnostic. Les caractéristiques cliniques ­ telles que l'âge, la fonction rénale, la fibrillation atriale, l'obésité et le sexe ­ modifient les taux de peptides natriurétiques et doivent être prises en compte dans l'interprétation. Chez les patients diabétiques, hypertendus et obèses, le dépistage précoce de l'IC par le dosage des peptides natriurétiques est crucial. De plus, ces peptides natriurétiques sont utiles pour le suivi des patients insuffisants cardiaques chroniques. Ils aident à confirmer une décompensation, à titrer le traitement, à en évaluer la réponse et à établir un pronostic. Cependant, il est essentiel de choisir un seul biomarqueur (BNP ou NT-proBNP) pour éviter toute confusion.

Colchicine in acute myocardial infarction: cardiovascular events at 1-year follow up.

OBJECTIVE: In 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. METHODS: This 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. RESULTS: At 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). CONCLUSIONS: There 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 NUMBER: NCT0315681.

Silent myocardial infarction fatty scars detected by coronary calcium score CT scan in diabetic patients without history of coronary heart disease.

OBJECTIVES: To evaluate the prevalence of intra-myocardial fatty scars (IMFS) most likely indicating previous silent myocardial infarction (SMI), as detected on coronary artery calcium (CAC) computed tomography (CT) scans in diabetic patients without history of coronary heart disease (CHD). METHODS: Diabetic patients screened for silent coronary insufficiency in a tertiary-care, university hospital between Jan-2015 and Dec-2016 were categorized according to their CAC score in two groups comprising 242 patients with CACS = 0 and 145 patients with CACS ≥ 300. CAC-CT scans were retrospectively evaluated for subendorcardial and transmural IMFS of the left ventricle. Adipose remodeling, patients' characteristics, cardiovascular risk factors and metabolic profile were compared between groups. RESULTS: Eighty-three (21%) patients with IMFS were identified, 55 (37.9%) in the group CACS ≥ 300 and 28 (11.6%) in the CACS = 0 (OR = 4.67; 95% CI = 2.78-7.84; p < 0.001). Total and average surface of IMFS and their number per patient were similar in both groups (p = 0.55; p = 0.29; p = 0.61, respectively). In the group CACS ≥ 300, patients with IMFS were older (p = 0.03) and had longer-lasting diabetes (p = 0.04). Patients with IMFS were older and had longer history of diabetes, reduced glomerular filtration rate, more coronary calcifications (all p < 0.05), and higher prevalence of carotid plaques (OR = 3.03; 95% CI = 1.43-6.39, p = 0.004). After correction for other variables, only a CACS ≥ 300 (OR = 5.12; 95% CI = 2.66-9.85; p < 0.001) was associated with an increased risk of having IMFS. CONCLUSIONS: In diabetic patients without known CHD, IMFSs were found in patients without coronary calcifications, although not as frequently as in patients with heavily calcified coronary arteries. It remains to be established if this marker translates in an upwards cardiovascular risk restratification especially in diabetic patients with CACS = 0. CLINICAL RELEVANCE STATEMENT: In diabetic patients without history of coronary heart disease, intramyocardial fatty scars, presumably of post-infarction origin, can be detected on coronary artery calcium CT scans more frequently, but not exclusively, if the coronary arteries are heavily calcified as compared to those without calcifications. KEY POINTS: • Intramyocardial fatty scars (IMFS), presumably of post-infarction origin, can be detected on coronary artery calcium (CAC) CT scans more frequently, but not exclusively, in diabetic patients with CACS ≥ 300 as compared to patients CACS = 0. • Patients with IMFS were older and had longer history of diabetes, reduced glomerular filtration rate, and more coronary calcifications. • Carotid plaques and CACS ≥ 300 were associated with an increased risk of having IMFS, about three and five folds respectively.

Comparison of healthcare costs before and after a STEMI: A French national health data system-based cohort study.

BACKGROUND: Few studies have investigated real-world healthcare costs following a myocardial infarction (MI) and, to our knowledge, none after an ST-elevation MI (STEMI) specifically. Producing such data is important in order to help evaluate the economic burden of STEMI, but also to feed economic evaluation models and eventually show the economic interest of reducing STEMI incidence. The aim of this study was to estimate the healthcare cost in the year preceding and the year following a STEMI in France, in order to estimate the surplus in healthcare resource consumption after a STEMI. METHODS: This study was conducted from the healthcare system perspective. The individual data from the HIBISCUS-STEMI cohort, which included patients with acute STEMI undergoing primary percutaneous coronary intervention, were matched with the French national health data system (Système National des Données de Santé, SNDS) using a probabilistic method. All expenses (in- and out-hospital) presented for reimbursement were taken into account to estimate a mean annual healthcare cost. RESULTS: A total 258 patients from the HIBISCUS-STEMI cohort were included in this economic study. The total mean healthcare cost was estimated at €3516 before the STEMI, and at €9980 after the STEMI. Hospitalizations constituted the largest cost item, 27 % of the total cost before the STEMI and 41.8 % after the STEMI (Δ + 338.8 %). Follow-up and rehabilitative care represented the second largest cost item (25.9 % before and 18 % after the STEMI, Δ + 96.7 %). Treatments represented 19.4 % of the total cost before the STEMI and 17.2 % after (Δ + 150.8 %). CONCLUSIONS: This study shows a significant surplus (threefold) of healthcare resource consumption in the year following a STEMI compared to the year preceding the STEMI.

Beta-blocker management in patients admitted for acute heart failure and reduced ejection fraction: a review and expert consensus opinion.

The role of the beta-adrenergic signaling pathway in heart failure (HF) is pivotal. Early blockade of this pathway with beta-blocker (BB) therapy is recommended as the first-line medication for patients with HF and reduced ejection fraction (HFrEF). Conversely, in patients with severe acute HF (AHF), including those with resolved cardiogenic shock (CS), BB initiation can be hazardous. There are very few data on the management of BB in these situations. The present expert consensus aims to review all published data on the use of BB in patients with severe decompensated AHF, with or without hemodynamic compromise, and proposes an expert-recommended practical algorithm for the prescription and monitoring of BB therapy in critical settings.

Pixel-wise statistical analysis of myocardial injury in STEMI patients with delayed enhancement MRI.

Objectives: Myocardial injury assessment from delayed enhancement magnetic resonance images is routinely limited to global descriptors such as size and transmurality. Statistical tools from computational anatomy can drastically improve this characterization, and refine the assessment of therapeutic procedures aiming at infarct size reduction. Based on these techniques, we propose a new characterization of myocardial injury up to the pixel resolution. We demonstrate it on the imaging data from the Minimalist Immediate Mechanical Intervention randomized clinical trial (MIMI: NCT01360242), which aimed at comparing immediate and delayed stenting in acute ST-Elevation Myocardial Infarction (STEMI) patients. Methods: We analyzed 123 patients from the MIMI trial (62 ± 12 years, 98 male, 65 immediate 58 delayed stenting). Early and late enhancement images were transported onto a common geometry using techniques inspired by statistical atlases, allowing pixel-wise comparisons across population subgroups. A practical visualization of lesion patterns against specific clinical and therapeutic characteristics was also proposed using state-of-the-art dimensionality reduction. Results: Infarct patterns were roughly comparable between the two treatments across the whole myocardium. Subtle but significant local differences were observed for the LCX and RCA territories with higher transmurality for delayed stenting at lateral and inferior/inferoseptal locations, respectively (15% and 23% of myocardial locations with a p-value <0.05, mainly in these regions). In contrast, global measurements were comparable for all territories (no statistically significant differences for all-except-one measurements before standardization / for all after standardization), although immediate stenting resulted in more subjects without reperfusion injury. Conclusion: Our approach substantially empowers the analysis of lesion patterns with standardized comparisons up to the pixel resolution, and may reveal subtle differences not accessible with global observations. On the MIMI trial data as illustrative case, it confirmed its general conclusions regarding the lack of benefit of delayed stenting, but revealed subgroups differences thanks to the standardized and finer analysis scale.

Prognostic impact of precipitated cardiac decompensation in symptomatic heart failure with reduced ejection fraction and severe secondary mitral regurgitation.

BACKGROUND: Our aim was to assess the distribution of primary (with no trigger) and secondary (with a decompensation trigger) heart failure events in a severe heart failure population and their association with 2-year all-cause mortality in the Mitra.Fr study. METHODS: We included 304 patients with symptomatic heart failure, and severe mitral regurgitation and guideline directed medical therapy randomized to medical therapy alone or medical therapy with percutaneous mitral valve repair. According to the follow-up, we defined 3 categories of events: follow-up without any heart failure event, at least 1 decompensation starting with a primary heart failure decompensation or starting with a precipitated secondary heart failure event. The primary outcome was 2-years all-cause mortality. RESULTS: A total of 179 patients (59 %) had at least 1 heart failure decompensation within 24-months of follow-up. 129 heart failure decompensations (72%) were a first primary heart failure and 50 (28%) were a first secondary decompensation. Finally, 30 patients had both types of decompensations but these were not taken into account for the comparison of primary and secondary decompensations. Primary decompensations were 3-times more frequent than secondary decompensations, but the mean number of heart failure decompensations was similar in the "Primary heart failure group" compared to the "Secondary heart failure group": (1.94 ± 1.39 vs 1.80 ± 1.07 respectively; P = .480). Compared to patients without heart failure decompensation, patients with "Only primary decompensation" or with "Only secondary decompensation" had a significantly increased risk of death (HR = 4.87, 95% CI [2.86, 8.32] and 2.68 95%CI [1.64, 4.37] respectively). All-cause mortality, was not significantly different between these 2 type of decompensations (HR = 1.82, 95% CI [0.93, 3.58]; P = .082), but each additional heart failure recurrence was associated with a significant increase in mortality risk (HR = 1.27, 95% CI [1.08; 1.50]; P = .005). CONCLUSIONS: In heart failure with reduced ejection fraction and severe secondary mitral regurgitation patients, primary heart failure decompensations were 3-times more frequent compared to precipitated decompensations with a nonsignificant trend in increased risk of all-cause mortality. Our results fail to support the differentiation between primary and secondary decompensations as they seem to portend the same outcome impact.

Pheochromocytoma-induced cardiogenic shock: A multicentre analysis of clinical profiles, management and outcomes.

OBJECTIVE: There is still uncertainty about the management of patients with pheochromocytoma-induced cardiogenic shock (PICS). This study aims to investigate the clinical presentation, management, and outcome of patients with PICS. METHODS: We collected, retrospectively, the data of 18 patients without previously known pheochromocytoma admitted to 8 European hospitals with a diagnosis of PICS. RESULTS: Among the 18 patients with a median age of 50 years (Q1-Q3: 40-61), 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension peaks and hypotension (72%). Echocardiography showed a median left ventricular ejection fraction (LVEF) of 25% (Q1-Q3: 15-33.5) with an atypical- Takotsubo (TTS) pattern in 50%. Inotropes/vasopressors were started in all patients and temporary mechanical circulatory support (t-MCS) was required in 11 (61%) patients. All patients underwent surgical removal of the pheochromocytoma; 4 patients (22%) were operated on while under t-MCS. The median LVEF was estimated at 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days. CONCLUSIONS: PICS should be suspected in case of a CS with severe cyclic blood pressure fluctuation and rapid hemodynamic deterioration, associated with increased inflammatory markers or in case of TTS progressing to CS, particularly if an atypical TTS echocardiographic pattern is revealed. T-MCS should be considered in the most severe cases. The main challenge is to stabilize the patient, with medical therapy or with t-MCS, since it remains a reversible cause of CS with a low mortality rate.

A Multimodal Cardioprotection Strategy During Cardiac Surgery: The ProCCard Study.

OBJECTIVE: The ProCCard study tested whether combining several cardioprotective interventions would reduce the myocardial and other biological and clinical damage in patients undergoing cardiac surgery. DESIGN: Prospective, randomized, controlled trial. SETTING: Multicenter tertiary care hospitals. PARTICIPANTS: 210 patients scheduled to undergo aortic valve surgery. INTERVENTIONS: A control group (standard of care) was compared to a treated group combining five perioperative cardioprotective techniques: anesthesia with sevoflurane, remote ischemic preconditioning, close intraoperative blood glucose control, moderate respiratory acidosis (pH 7.30) just before aortic unclamping (concept of the "pH paradox"), and gentle reperfusion just after aortic unclamping. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the postoperative 72-h area under the curve (AUC) for high-sensitivity cardiac troponin I (hsTnI). Secondary endpoints were biological markers and clinical events occurring during the 30 postoperative days and the prespecified subgroup analyses. The linear relationship between the 72-h AUC for hsTnI and aortic clamping time, significant in both groups (p < 0.0001), was not modified by the treatment (p = 0.57). The rate of adverse events at 30 days was identical. A non-significant reduction of the 72-h AUC for hsTnI (-24%, p = 0.15) was observed when sevoflurane was administered during cardiopulmonary bypass (46% of patients in the treated group). The incidence of postoperative renal failure was not reduced (p = 0.104). CONCLUSION: This multimodal cardioprotection has not demonstrated any biological or clinical benefit during cardiac surgery. The cardio- and reno-protective effects of sevoflurane and remote ischemic preconditioning therefore remain to be demonstrated in this context.

Cardioprotective effects of shock wave therapy: A cardiac magnetic resonance imaging study on acute ischemia-reperfusion injury.

Introduction: Cardioprotection strategies remain a new frontier in treating acute myocardial infarction (AMI), aiming at further protect the myocardium from the ischemia-reperfusion damage. Therefore, we aimed at investigating the mechano-transduction effects induced by shock waves (SW) therapy at time of the ischemia reperfusion as a non-invasive cardioprotective innovative approach to trigger healing molecular mechanisms. Methods: We evaluated the SW therapy effects in an open-chest pig ischemia-reperfusion (IR) model, with quantitative cardiac Magnetic Resonance (MR) imaging performed along the experiments at multiple time points (baseline (B), during ischemia (I), at early reperfusion (ER) (∼15 min), and late reperfusion (LR) (3 h)). AMI was obtained by a left anterior artery temporary occlusion (50 min) in 18 pigs (32 ± 1.9 kg) randomized into SW therapy and control groups. In the SW therapy group, treatment was started at the end of the ischemia period and extended during early reperfusion (600 + 1,200 shots @0.09 J/mm2, f = 5 Hz). The MR protocol included at all time points LV global function assessment, regional strain quantification, native T1 and T2 parametric mapping. Then, after contrast injection (gadolinium), we obtained late gadolinium imaging and extra-cellular volume (ECV) mapping. Before animal sacrifice, Evans blue dye was administrated after re-occlusion for area-at-risk sizing. Results: During ischemia, LVEF decreased in both groups (25 ± 4.8% in controls (p = 0.031), 31.6 ± 3.2% in SW (p = 0.02). After reperfusion, left ventricular ejection fraction (LVEF) remained significantly decreased in controls (39.9 ± 4% at LR vs. 60 ± 5% at baseline (p = 0.02). In the SW group, LVEF increased quickly ER (43.7 ± 11.4% vs. 52.4 ± 8.2%), and further improved at LR (49.4 ± 10.1) (ER vs. LR p = 0.05), close to baseline reference (LR vs. B p = 0.92). Furthermore, there was no significant difference in myocardial relaxation time (i.e. edema) after reperfusion in the intervention group compared to the control group: ΔT1 (MI vs. remote) was increased by 23.2±% for SW vs. +25.2% for the controls, while ΔT2 (MI vs. remote) increased by +24.9% for SW vs. +21.7% for the control group. Discussion: In conclusion, we showed in an ischemia-reperfusion open-chest swine model that SW therapy, when applied near the relief of 50' LAD occlusion, led to a nearly immediate cardioprotective effect translating to a reduction in the acute ischemia-reperfusion lesion size and to a significant LV function improvement. These new and promising results related to the multi-targeted effects of SW therapy in IR injury need to be confirmed by further in-vivo studies in close chest models with longitudinal follow-up.

Outcome of patients admitted with oxygen mismatch and myocardial injury or infarction in emergency departments.

AIMS: To describe the outcomes and associated factors in a population of patients admitted to emergency departments with at least one condition of oxygen supply/demand imbalance, regardless of the troponin result or restrictive criteria for type 2 myocardial infarction. METHODS: We constituted a retrospective cohort of 824 patients. Medical records of patients having undergone a troponin assay were reviewed for selection and classification, and data including in-hospital stay and readmissions were collected. The reported outcomes are in-hospital mortality, 3-year mortality, and major adverse cardiovascular events. RESULTS: Patients with myocardial infarction or injury, either chronic or acute, were older, with more history of hypertension and chronic heart or renal failure but not for other cardiovascular risk factors and medical history. Acute myocardial injury and type 2 myocardial infarction were significantly associated with in-hospital mortality [odds ratio (OR) 3.71 95% confidence interval (CI) 1.90-7.33 and OR 3.15 95% CI 1.59-6.28, respectively]. However, the long-term mortality does not differ in comparison with patients presenting chronic myocardial injury or nonelevated troponin, ranging from 26.9 to 34.3%. Patients with chronic myocardial injury and type 2 myocardial infarction had more long-term major cardiovascular events (39.3 and 38.8%), but only for acute heart failure, and none was associated with this outcome after adjustment. CONCLUSION: Among patients admitted to emergency departments with an oxygen supply/demand imbalance, acute myocardial injury and type 2 myocardial infarction are strongly associated with in-hospital mortality. However, they are not associated with higher long-term mortality or major cardiovascular events after discharge, which tend to occur in elderly people with comorbidities.

Challenges and Opportunities in Titrating Disease-Modifying Therapies in Heart Failure with Reduced Ejection Fraction and Chronic Kidney Disease.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is highly prevalent in patients with heart failure and reduced ejection fraction (HFrEF), representing a major factor of adverse outcomes. In clinical practice, it is one of the main reasons for not initiating, not titrating, and even withdrawing efficient heart failure drug therapies in patients. RECENT FINDINGS: Despite limited data, studies show that HFrEF therapies maintain their benefits on cardiovascular outcomes in patients with CKD. Most HF drugs cause acute renal haemodynamic changes, but with stabilisation or even improvement after the acute phase, thus with no long-term worsening of the renal function. In this expert opinion-based paper, we challenge the pathophysiology misunderstandings that impede HF disease-modifying therapy implementation in this setting and propose a strategy for HF drug titration in patients with moderate, severe, and end-stage chronic kidney disease.

Anti-Inflammatory Drug Candidates for Prevention and Treatment of Cardiovascular 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.

Elaboration of a French version of the Duke Activity Status Index questionnaire and performance to predict functional capacity.

BACKGROUND: Guidelines recommend detecting poor functional capacity (VO2max < 14 ml.kg-1.min-1) to assess preoperative cardiac risk. This screening is performed via a cardiopulmonary exercise test (CPET), the self-reported inability to climb two flights of stairs, or the use of the Duke Activity Status Index (DASI) questionnaire, which has shown a significant correlation with VO2max and postoperative outcomes. The objectives of the present study were: 1) to create a French version of the DASI questionnaire (FDASI); 2) to assess its diagnostic performance in predicting functional capacity. METHODS: Consecutive adult patients undergoing CPET for medical or preoperative evaluation were prospectively included between May 2020 and March 2021. All patients were asked to complete FDASI as a self-questionnaire and report their inability to climb two flights of stairs. RESULTS: 122 patients were included. Test-retest reliability was 0.88 and 23 (19%) patients experienced a VO2max < 14 ml.kg-1.min-1. There was a significant positive relationship between FDASI and VO2max: r2 = 0.32; p < 0.001. ROCAUC was 0.81 [95%CI: 0.73-0.89]. The best FDASI score threshold was 36 points, leading to sensitivity and specificity values of 87% [74-100] and 68% [56-79], respectively. Besides, sensitivity and specificity were 35% [17-56] and 92% [86-97] for the self-reported inability to climb two flights of stairs. CONCLUSION: A FDASI score of 36 represents a reliable threshold the clinicians could routinely use to identify patients with a VO2max < 14 ml.kg-1.min-1. FDASI could advantageously replace the self-reported inability to climb two flights of stairs.

Sequencing and titrating approach of therapy in heart failure with reduced ejection fraction following the 2021 European Society of Cardiology guidelines: an international cardiology survey.

AIMS: In symptomatic patients with heart failure and reduced ejection fraction (HFrEF), recent international guidelines recommend initiating four major therapeutic classes rather than sequential initiation. It remains unclear how this change in guidelines is perceived by practicing cardiologists versus heart failure (HF) specialists. METHODS AND RESULTS: An independent academic web-based survey was designed by a group of HF specialists and posted by email and through various social networks to a broad community of cardiologists worldwide 1 year after the publication of the latest European HF guidelines. Overall, 615 cardiologists (38 [32-47] years old, 63% male) completed the survey, of which 58% were working in a university hospital and 26% were HF specialists. The threshold to define HFrEF was ≤40% for 61% of the physicians. Preferred drug prescription for the sequential approach was angiotensin-converting enzyme inhibitors or angiotensin receptor-neprilysin inhibitors first (74%), beta-blockers second (55%), mineralocorticoid receptor antagonists third (52%), and sodium-glucose cotransporter 2 inhibitors (53%) fourth. Eighty-four percent of participants felt that starting all four classes was feasible within the initial hospitalization, and 58% felt that titration is less important than introducing a new class. Age, status in training, and specialization in HF field were the principal characteristics that significantly impacted the answers. CONCLUSION: In a broad international cardiology community, the 'historical approach' to HFrEF therapies remains the preferred sequencing approach. However, accelerated introduction and uptitration are also major treatment goals. Strategy trials in treatment guidance are needed to further change practices.