Association of Circulating Autophagy Proteins ATG5 and Beclin 1 with Acute Myocardial Infarction in a Case-Control Study.

INTRODUCTION: Acute myocardial infarction (AMI) is a main contributor of sudden cardiac death worldwide. The discovery of new biomarkers that can improve AMI risk prediction meets a major clinical need for the identification of high-risk patients and the tailoring of medical treatment. Previously, we reported that autophagy a highly conserved catabolic mechanism for intracellular degradation of cellular components is involved in atherosclerotic plaque phenotype and cardiac pathological remodeling. The crucial role of autophagy in the normal and diseased heart has been well described, and its activation functions as a pro-survival process in response to myocardial ischemia. However, autophagy is dysregulated in ischemia/reperfusion injury, thus promoting necrotic or apoptotic cardiac cell death. Very few studies have focused on the plasma levels of autophagy markers in cardiovascular disease patients, even though they could be companion biomarkers of AMI injury. The aims of the present study were to evaluate (1) whether variations in plasma levels of two key autophagy regulators autophagy-related gene 5 (ATG5) and Beclin 1 (the mammalian yeast ortholog Atg6/Vps30) are associated with AMI and (2) their potential for predicting AMI risk. METHODS: The case-control study population included AMI patients (n = 100) and control subjects (n = 99) at high cardiovascular risk but without known coronary disease. Plasma levels of ATG5 and Beclin 1 were measured in the whole population study by enzyme-linked immunosorbent assay. RESULTS: Multivariate analyses adjusted on common cardiovascular factors and medical treatments, and receiver operating characteristic curves demonstrated that ATG5 and Beclin 1 levels were inversely associated with AMI and provided original biomarkers for AMI risk prediction. CONCLUSION: Plasma levels of autophagy regulators ATG5 and Beclin 1 represent relevant candidate biomarkers associated with AMI.

Clinical Implications of CT-detected Hypoattenuation Thickening on Left Atrial Appendage Occlusion Devices.

Background At follow-up CT after left atrial appendage occlusion (LAAO), hypoattenuation thickening (HAT) on the atrial aspect of the device is a common finding but the clinical implications require further study. Purpose To assess the association of HAT grade at follow-up CT with clinical characteristics and outcomes in patients who underwent LAAO. Materials and Methods This prospective study included consecutive participants with atrial fibrillation and who were at high risk for stroke (CHA2DS2-VASc score ≥4) who underwent LAAO and were administered pacifier or nonpacifier devices at two French medical centers between January 2012 and November 2020. Postprocedure CT images were evaluated by two radiologists in consensus and device-specific interpretation algorithms were applied to classify HAT as low grade (low suspicion of thrombosis) or high grade (high suspicion of thrombosis). The association between HAT grade and clinical characteristics was assessed using multinomial logistic regression, and variables associated with risk of stroke were assessed using a Cox proportional hazard model. Results This study included 412 participants (mean age, 76 years ± 8 [SD]; 284 male participants) who underwent follow-up CT at a mean of 4.2 months ± 1.7 after LAAO. Low-grade and high-grade HAT were depicted in 98 of 412 (23.8%) and 21 of 412 (5.1%) participants, respectively. High-grade HAT was associated with higher odds of antithrombotic drug discontinuation during follow-up (odds ratio, 9.5; 95% CI: 3.1, 29.1; P < .001), whereas low-grade HAT was associated with lower odds of persisting left atrial appendage patency (odds ratio, 0.46; 95% CI: 0.27, 0.79; P = .005). During a median follow-up of 17 months (IQR, 11-41 months), stroke occurred in 24 of 412 (5.8%) participants. High-grade HAT was associated with stroke (hazard ratio, 4.6; 95% CI: 1.5, 14.0; P = .008) and low-grade HAT (P = .62) was not. Conclusion Low-grade HAT was a more common finding at CT performed after LAAO CT (24%) than was high-grade HAT (5%), but it was associated with more favorable outcomes than high-grade HAT, which was associated with higher stroke risk. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Choe in this issue.

Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is a clinical condition of transient acute heart failure correlated to regional wall motion abnormalities extending beyond the distribution of a single epicardial coronary artery. It is classified into four major types: apical, basal, mid-ventricular and focal. Sympathetic nerve stimulation and catecholamine storm are the main players in the pathogenesis of TTC. The clinical course of disease is generally benign but it may end with life-threatening complications. Coronary angiography, left ventriculogram, transthoracic echocardiography and cardiac magnetic resonance imaging (CMR) are the main tools for making diagnosis. Except for critical cases with hemodynamic instability and/or complications, the overall management is limited to conventional heart failure therapy.

Impact of Coronary Artery Disease and Percutaneous Coronary Intervention on Transcatheter Aortic Valve Implantation.

INTRODUCTION: The prevalence of coronary artery disease (CAD) detected in preoperative work-up for transcatheter aortic valve implantation (TAVI) is high. Instead, the management of a concomitant CAD remains unclear. We evaluate the impact of CAD and percutaneous coronary intervention (PCI) on TAVI procedures. MATERIALS AND METHODS: A retrospective study was conducted on 1336 consecutive patients who underwent TAVI in Toulouse University Hospital, Rangueil, France. The studied population was divided into 2 groups: CAD-TAVI group and No CAD-TAVI group. Then, the CAD-TAVI group was segregated into 2 subgroups: PCI-TAVI group and No PCI-TAVI group. In-hospital adverse clinical outcomes were assessed in each group. RESULTS: Pre-TAVI work-up revealed significant CAD in 36% of 1030 patients eligible for inclusion in the study. The overall prevalence of in-hospital death, stroke, major or life-threatening bleeding, minor bleeding, major vascular complications, minor vascular complications, pacemaker implantation, and acute kidney injury was 2.7%, 2.4%, 2.8%, 3.6%, 3.9%, 7.5%, 12.5%, and 2.7%, respectively. Among the studied population, 55% were admitted to the cardiac care unit. No significant statistical difference was observed between groups. Discussion. CAD-TAVI population was not more likely to develop in-hospital adverse clinical outcomes post-TAVI procedure compared to others. Also, no significant difference regarding in-hospital death was observed. In parallel, performing PCI prior to TAVI did not increase the risk of in-hospital death and complications. The difference in terms of the distribution of antithrombotic regimen may explain the higher prevalence of bleeding events in the PCI-TAVI group. CONCLUSION: This study provides direct clinical relevance useful in daily practice. No negative impact has been attributed to the presence of a concomitant CAD and/or preoperative PCI on the TAVI hospitalization period.

Prevalence of Posttranscatheter Aortic Valve Implantation Vascular Complications in Real Life.

BACKGROUND: Vascular complications (VCs) are commonly observed after transfemoral transcatheter aortic valve implantation (TAVI) procedures. Closure devices for the access site were developed to reduce their incidence. We aim to evaluate the prevalence, predictors, and outcomes of the occurrence of post-TAVI VCs. MATERIALS AND METHODS: A retrospective study was conducted on 1336 consecutive patients who underwent TAVI at the University Hospital of Toulouse, France, between January 2016 and March 2020. All included procedures were performed through the common femoral artery, and ProGlide® was the used closure device. The studied population was divided into two groups depending on the occurrence of VCs defined according to Valve Academic Research Consortium-2 criteria. RESULTS: The mean age of the studied population was 84.4 ± 6.9, and 48% were male. 90% of TAVI interventions were performed through the right femoral artery. The prevalence of VCs was 18.8%, and 3.7% were major. Prolonged procedure duration was an independent predictor of VCs. Using the right access site and smaller introducer size (14 Fr) were preventive factors. No significant difference in mortality rate was detected between the two groups. CONCLUSION: This study showed a low prevalence for post-TAVI VCs, especially for the major type. An increase in bleeding events and prolonged cardiac care unit stay were the common adverse outcomes.

Colchicine for Left Ventricular Infarct Size Reduction in Acute Myocardial Infarction: A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Protocol - The COVERT-MI Study.

Inflammatory processes have been identified as key mediators of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI). They add damage to the myocardium and are associated with clinical adverse events (heart failure and cardiovascular death) and poor myocardial recovery. Colchicine is a well-known alkaloid with potent anti-inflammatory properties. In a proof-of-concept phase II trial, colchicine has been associated with a significant 50% reduction of infarct size (assessed by creatine kinase levels) in comparison to placebo in acute STEMI patients referred for primary percutaneous coronary intervention (PPCI). The Colchicine in STEMI Patients Study (COVERT-MI) is an ongoing confirmative prospective, multicenter, randomized, double-blind trial testing whether a short course oral treatment with colchicine versus placebo decreases myocardial injury in patients presenting with STEMI referred for PPCI. Adult patients, with a first STEMI episode and an initial TIMI flow ≤1, referred for PPCI, will be randomized (n = 194) in a 1:1 ratio to receive an oral bolus of colchicine of 2 mg followed by 0.5 mg b.i.d. treatment during 5 days or matching placebo. The primary endpoint will be the reduction in infarct size as assessed by cardiac magnetic resonance at 5 ± 2 days between both groups. The main secondary endpoints will be tested between groups in hierarchical order with left ventricular ejection fraction at 5 days, microvascular obstruction presence at 5 days, and absolute adverse left ventricular remodeling between 5 days and 3 months. This academic study is being financed by a grant from the French Ministry of Health (PHRCN-16-0357). Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present study describes the rationale, design, and methods of the trial.

Evaluation of Mitral and Aortic Valvular Disease and Left Ventricular Dysfunction in a Lebanese Population: Retrospective Single-Center Experience.

BACKGROUND Recently, new therapeutic approaches have revolutionized the management of left ventricular dysfunction (LVD) and valvular heart disease (VHD), which are a growing public health problem. In parallel, there are no available epidemiological data about LVD and VHD in developing countries, especially in the Mediterranean area. This retrospective study was conducted at a single center and aimed to evaluate the associations between mitral and aortic valvular disease and left ventricle systolic and diastolic dysfunction in the Lebanese population. MATERIAL AND METHODS A retrospective study was conducted of 4520 consecutive patients aged >18 years who were referred to the Cardiovascular Department of Notre Dame de Secours-University Hospital in Jbeil-Lebanon for transthoracic echocardiography between December 2016 and December 2019. The study population was divided into different groups based on types of LVD and VHD. Left ventricle systolic dysfunction was defined as a left ventricle ejection fraction (EF) ≤40%. Statistical analysis was carried out using SPSS software version 20. RESULTS VHD and systolic dysfunction were more common in men, whereas diastolic dysfunction was more common in women. Being older than age 65 years and smoking were significantly associated with heart failure with preserved EF, whereas female sex was a significant preventive factor against heart failure with reduced EF. Systemic hypertension was correlated with mitral stenosis and tricuspid regurgitation, whereas diabetes mellitus was associated with tricuspid regurgitation (TR). Smoking and older age also appeared to be associated with aortic stenosis. CONCLUSIONS Mitral valve disease (regurgitation and stenosis) was significantly correlated with systolic dysfunction, whereas aortic and mitral regurgitation were associated with diastolic dysfunction. Better monitoring of cardiovascular disease risk factors may lead to a reduced burden of LVD and VHD.

Participating in Sports After Mitral Valve Repair for Primary Mitral Regurgitation: A Retrospective Cohort Study.

OBJECTIVE: Participating in either competitive or leisure sports is restrictive after surgical mitral valve repair (MVR). In this study, we examine the impact of sports on outcomes after MVR. DESIGN: Retrospective cohort study. SETTING: Patients aged 18 to 65 years who underwent a first-time MVR for primary mitral regurgitation (MR) in a tertiary care center. PATIENTS: One hundred twenty-one consecutive patients were included in the study. The exclusion criteria were as follows: other concomitant procedures, early perioperative death or repeat intervention, noncardiac death or endocarditis during follow-up, and general contraindications for normal physical activity. ASSESSMENT OF RISK FACTORS: Participation in sports was quantified by the number of hours per week during the past 6 months, classified according to the Mitchell classification and assessed with the International Physical Activity Questionnaire (IPAQ) short form. MAIN OUTCOME MEASURES: The primary composite endpoint was MVR failure defined as MR grade ≥2 or mean transmitral gradient ≥8 mm Hg, signs and symptoms of heart failure, or late-onset postoperative AF (>3 months). RESULTS: The mean age was 50 ± 11 years, and there were 85 (71%) men. The median follow-up was 34 months [interquartile range (IQR): 20-50]. Fifty-six (46%) patients participated in sports regularly (median of 3 h/wk; IQR: 2-5). Twenty (17%) patients reached the primary composite endpoint with no correlation with participation in sports (P = 0.537), IPAQ categories (P = 0.849), in any of the Mitchell classification subgroups and a high level of participation in sports ≥6 hours (P = 0.679). CONCLUSIONS: Sports seem to be unrelated to the worst outcome after MVR.

Coronary Artery Spasm: New Insights.

Coronary artery spasm (CAS) defined by a severe reversible diffuse or focal vasoconstriction is the most common diagnosis among INOCA (ischemia with no obstructive coronary artery disease) patients irrespective to racial, genetic, and geographic variations. However, the prevalence of CAS tends to decrease in correlation with the increasing use of medicines such as calcium channel blockers, angiotensin converting enzyme inhibitor, and statins, the controlling management of atherosclerotic risk factors, and the decreased habitude to perform a functional reactivity test in highly active cardiac catheterization centers. A wide spectrum of clinical manifestations from silent disease to sudden cardiac death was attributed to this complex entity with unclear pathophysiology. Multiple mechanisms such as the autonomic nervous system, endothelial dysfunction, chronic inflammation, oxidative stress, and smooth muscle hypercontractility are involved. Regardless of the limited benefits proffered by the newly emerged cardiac imaging modalities, the provocative test remains the cornerstone diagnostic tool for CAS. It allows to reproduce CAS and to evaluate reactivity to nitrates. Different invasive and noninvasive therapeutic approaches are approved for the management of CAS. Long-acting nondihydropyridine calcium channel blockers are recommended for first line therapy. Invasive strategies such as PCI (percutaneous coronary intervention) and CABG (coronary artery bypass graft) have shown benefits in CAS with significant atherosclerotic lesions. Combination therapies are proposed for refractory cases.

Twenty-year trends in profile, management and outcomes of patients with ST-segment elevation myocardial infarction according to use of reperfusion therapy: Data from the FAST-MI program 1995-2015.

The increased use of reperfusion therapy in ST-segment-elevation myocardial infarction (STEMI) patients in the past decades is generally considered the main determinant of improved outcomes. The aim was to assess 20-year trends in profile, management, and one-year outcomes in STEMI patients in relation with use or non-use of reperfusion therapy (primary percutaneous coronary intervention (pPCI) or fibrinolysis). METHODS: We used data from 5 one-month French nationwide registries, conducted 5 years apart from 2005 to 2015, including 8579 STEMI patients (67% with and 33% without reperfusion therapy) admitted to cardiac intensive care units in France. RESULTS: Use of reperfusion therapy increased from 49% in 1995 to 82% in 2015, with a shift from fibrinolysis (37.5% to 6%) to pPCI (12% to 76%). Early use of evidence-based medications gradually increased over the period in both patients with and without reperfusion therapy, although it remained lower at all times in those without reperfusion therapy. One-year mortality decreased in patients with reperfusion therapy (from 11.9% in 1995 to 5.9% in 2010 and 2015, hazard ratio [HR] adjusted on baseline profile 0.40; 95% CI: 0.29-0.54, P < .001) and in those without reperfusion therapy (from 25.0% to 18.2% in 2010 and 8.1% in 2015, HR: 0.33; 95% CI: 0.24-0.47, P < .001). CONCLUSIONS: In STEMI patients, one-year mortality continues to decline, both related to increased use of reperfusion therapy and progress in overall patient management. In patients with reperfusion therapy, mortality has remained stable since 2010, while it has continued to decline in patients without reperfusion therapy.

Short- and Mid-Term Prognosis of Patients Undergoing Rotational Atherectomy in Aortoostial Coronary Lesions in Left Main or Right Coronary Arteries.

OBJECTIVE: To determine short-term and mid-term prognosis in patients with calcified ostial coronary lesions who underwent rotational atherectomy (RA). BACKGROUND: RA was developed to facilitate stenting in complex lesions. Treatment of calcified aortoostial coronary lesions with RA appears to have poorer procedure outcomes than nonostial lesions; yet the literature on this topic is scarce. METHODS: Of 498 consecutive patients who underwent RA, a total of 80 (16.1%) presented with aortoostial lesions. A comparative, monocentric study was performed between patients with aortoostial and nonaortoostial stenosis, in a retrospective registry. The primary endpoint was the procedural success rate. Secondary endpoints were the rates of major adverse cardiac and cardiovascular events (MACE) at 30 days and 24 months. RESULTS: The procedural success rate was high and similar in patients with and without ostial lesions (96.3% vs 94.7%, p=0.78), as was the rate of angiographic complications (7.5% vs 8.4%, p=0.80). However, the 30-day mortality rate was significantly higher in the aortoostial group (11.3% vs 4.8%, p=0.04), as was the 24-month rate of MACE (43.8% vs 31.8%, p=0.04). The aortoostial location of the lesion was an independent factor associated with the occurrence of cardiovascular events at 24 months (HR = 1.52, 95% CI, 1.03-2.26, p=0.035). CONCLUSION: Procedural success and complication rates were similar in patients with and without aortoostial lesions. Despite a poor short- and mid-term prognosis, rotational atherectomy appears to be a feasible and safe treatment option for calcified aortoostial coronary lesions.

Acute Myocardial Infarction: Changes in Patient Characteristics, Management, and 6-Month Outcomes Over a Period of 20 Years in the FAST-MI Program (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) 1995 to 2015.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. METHODS: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14 423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. RESULTS: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ≤72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. CONCLUSIONS: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.

Long-term outcomes of rotational atherectomy of underexpanded stents. A single center experience.

OBJECTIVES: To analyze the procedural and long-term outcomes of the use of rotational atherectomy (RA) in underexpanded stents in our cohort and to provide an overview of currently available data on this technique. BACKGROUND: Stent underexpansion (SU) has been related to stent thrombosis and restenosis. RA has been used to treat undilatable SU as a bail-out strategy with encouraging results. METHODS: This is an observational, single-center study. We included patients who underwent stentablation between 2013 and 2017. Baseline demographics, procedural results, in-hospital major adverse cardiac events (MACE), and long-term follow-up MACE were retrospectively collected. RESULTS: A total of 11 patients (90.9% males, mean age 65.4 ± 18.6) were included in this study. Median left ventricle ejection fraction was 53.5% [46.2-55]. Median calculated Syntax score was 16 [9-31] and 45.5% of patients were admitted for acute coronary syndrome. Radial approach was used in 63.6% of cases. Most patients only required one burr (45% used a 1.5 mm diameter burr) during the intervention. Procedural success was achieved in 90.9% of the cases. Acute lumen gain was 42.7% [30.7-61.49]. There were no in-hospital deaths or MACE. At a median follow-up of 26 months, only one patient (9.1%) suffered MACE in the context of acute coronary syndrome, and two patients (18.2%) required non-target lesion revascularization. No deaths were reported. CONCLUSIONS: RA of under expanded stents is a feasible option with a high rate of procedural success. At long-term follow-up, all of them were alive and 90.9% of patients remained free from MACE.

Outcomes after use of covered stents to treat coronary artery perforations. Comparison of old and new-generation covered stents.

OBJECTIVES: To compare outcomes in patients receiving polytetrafluoroethylene (PTFE) and polyurethane (PL) covered stents (CS) after coronary artery perforation (CAP). BACKGROUND: The prognosis of CAP has improved with the advent of CSs. Information is scarce about the outcomes of new-generation CSs. METHODS: Sixty-one patients were treated with CSs in a 5-years period (age = 77 ± 8.75% males). Procedural and clinical data were retrospectively collected. The primary endpoint was procedural success. Secondary endpoints included death and major adverse cardiac events (MACE) defined as a composite of death, myocardial infarction, target vessel, and lesion revascularization and need for surgical repair). RESULTS: Twenty-two (36%) received PL-CSs and 39 (65%) PTFE-CSs. There were no differences in procedural success (86% vs 69%, P = 0.216). Time to deliver was shorter with PL-CS despite larger length of stents (8[11] vs 15[16] min, P = 0.001; 20[5] vs 16[3] mm, P < 0.001). This group had lower rate of pericardial effusion and cardiac arrest (41% vs 72%, P = 0.028; 5% vs 26%, P = 0.045). At 1-year follow-up, MACE rates were similar (58% vs 56%, P = 1.000) with atrend toward TVR in the PL-CS arm (21% vs 5%, P = 0.083). No differences were found in mortality (26% vs 41%, P = 0.385). Each group had 1 stent thrombosis and in-stent restenosis trended higher in the PL-CS group (12% vs 3%, P = 0.223). CONCLUSIONS: Time to deliver was shorter with the PL-CS and resulted in lower rate of pericardial effusion and cardiac arrest. However, there were no significant differences in procedural success and 1-year follow-up MACE in patients treated with PL-CS or PTFE-CS.

Incidence and Significance of Spontaneous ST Segment Re-elevation After Reperfused Anterior Acute Myocardial Infarction　- Relationship With Infarct Size, Adverse Remodeling, and Events at 1 Year.

BACKGROUND: Up to 25% of patients with ST elevation myocardial infarction (STEMI) have ST segment re-elevation after initial regression post-reperfusion and there are few data regarding its prognostic significance.Methods and Results:A standard 12-lead electrocardiogram (ECG) was recorded in 662 patients with anterior STEMI referred for primary percutaneous coronary intervention (PPCI). ECGs were recorded 60-90 min after PPCI and at discharge. ST segment re-elevation was defined as a ≥0.1-mV increase in STMax between the post-PPCI and discharge ECGs. Infarct size (assessed as creatine kinase [CK] peak), echocardiography at baseline and follow-up, and all-cause death and heart failure events at 1 year were assessed. In all, 128 patients (19%) had ST segment re-elevation. There was no difference between patients with and without re-elevation in infarct size (CK peak [mean±SD] 4,231±2,656 vs. 3,993±2,819 IU/L; P=0.402), left ventricular (LV) ejection fraction (50.7±11.6% vs. 52.2±10.8%; P=0.186), LV adverse remodeling (20.1±38.9% vs. 18.3±30.9%; P=0.631), or all-cause mortality and heart failure events (22 [19.8%] vs. 106 [19.2%]; P=0.887) at 1 year. CONCLUSIONS: Among anterior STEMI patients treated by PPCI, ST segment re-elevation was present in 19% and was not associated with increased infarct size or major adverse events at 1 year.

Myocardial multilayer strain does not provide additional value for detection of myocardial viability assessed by SPECT imaging over and beyond standard strain.

BACKGROUND: The aim of this study was to evaluate the value of multilayer strain analysis to the assessment of myocardial viability (MV) through the comparison of both speckle tracking echocardiography and single-photon emission computed tomography (SPECT) imaging. We also intended to determine which segmental longitudinal strain (LS) cutoff value would be optimal to discriminate viable myocardium. METHODS: We included 47 patients (average age: 61 ± 11 years) referred to our cardiac imaging center for MV evaluation. All patients underwent transthoracic echocardiography with measures of LS, SPECT, and coronary angiography. RESULTS: In all, 799 segments were analyzed. We correlated myocardial tracer uptake by SPECT with sub-endocardial, sub-epicardial, and mid-segmental LS values with r = .514 P < .0001, r = .501 P < .0001, and r = .520 P < .0001, respectively. The measurements of each layer strain (sub-endocardial, sub-epicardial, and mid) had the same performance to predict MV viability as defined by SPECT with areas under curve of 0.819 [0.778-0.861, P < .0001], 0.809 [0.764-0.854, P < .0001], and 0.817 [0.773-0.860, P < .0001], respectively. The receiver-operating characteristic analysis yielded a cutoff value of -6.5% for mid-segmental LS with a sensitivity of 76% and specificity of 76% to predict segmental MV as defined by SPECT. CONCLUSIONS: Multilayer strain analysis does not evaluate MV with more accuracy than standard segmental LS analysis.

Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study.

BACKGROUND: Epidemiological and observational studies have established that high-density lipoprotein cholesterol (HDL-C) is an independent negative cardiovascular risk factor. However, simple measurement of HDL-C levels is no longer sufficient for cardiovascular risk assessment. Therefore, there is a critical need for novel non-invasive biomarkers that would display prognostic superiority over HDL-C. Cell surface ecto-F1-ATPase contributes to several athero-protective properties of HDL, including reverse cholesterol transport and vascular endothelial protection. Serum inhibitory factor 1 (IF1), an endogenous inhibitor of ecto-F1-ATPase, is an independent determinant of HDL-C associated with low risk of coronary artery disease (CAD). This work aimed to examine the predictive value of serum IF1 for long-term mortality in CAD patients. Its informative value was compared to that of HDL-C. METHOD: Serum IF1 levels were measured in 577 male participants with stable CAD (age 45-74 years) from the GENES (Genetique et ENvironnement en Europe du Sud) study. Vital status was yearly assessed, with a median follow-up of 11 years and a 29.5 % mortality rate. Cardiovascular mortality accounted for the majority (62.4 %) of deaths. RESULTS: IF1 levels were positively correlated with HDL-C (r s = 0.40; P < 0.001) and negatively with triglycerides (r s = -0.21, P < 0.001) and CAD severity documented by the Gensini score (r s = -0.13; P < 0.01). Total and cardiovascular mortality were lower at the highest quartiles of IF1 (HR = 0.55; 95 % CI, 0.38-0.89 and 0.50 (0.28-0.89), respectively) but not according to HDL-C. Inverse associations of IF1 with mortality remained significant, after multivariate adjustments for classical cardiovascular risk factors (age, smoking, physical activity, waist circumference, HDL-C, dyslipidemia, hypertension, and diabetes) and for powerful biological and clinical variables of prognosis, including heart rate, ankle-brachial index and biomarkers of cardiac diseases. The 10-year mortality was 28.5 % in patients with low IF1 (<0.42 mg/L) and 21.4 % in those with high IF1 (≥0.42 mg/L, P < 0.02). CONCLUSIONS: We investigated for the first time the relation between IF1 levels and long-term prognosis in CAD patients, and found an independent negative association. IF1 measurement might be used as a novel HDL-related biomarker to better stratify risk in populations at high risk or in the setting of pharmacotherapy.

Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial).

BACKGROUND: Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. METHODS: CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. RESULTS: Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. CONCLUSIONS: The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.