Cyclosporine before PCI in Patients with Acute Myocardial Infarction.

BACKGROUND: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

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.

Incremental predictive value of carotid ultrasonography in the assessment of coronary risk in a cohort of asymptomatic type 2 diabetic subjects.

OBJECTIVE: Consensus guidelines recommend cardiovascular risk assessment as the initial step of primary prevention. The aim of this study was to evaluate the incremental predictive value for coronary events conferred by carotid ultrasonography in addition to risk assessment by Framingham score and screening for silent myocardial ischemia in a cohort of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We prospectively studied 229 patients free of any cardiovascular complication with at least one additional cardiovascular risk factor. At baseline, all patients had an exercise treadmill test, carotid intima-media thickness (IMT) measurement, and coronary risk assessment by Framingham score. Cardiovascular events were registered during a 5-year follow-up period. RESULTS: Age, carotid IMT, carotid plaques, number of risk factors, Framingham score, and suboptimal exercise electrocardiogram were associated with incident cardiovascular events (P < 0.05). Carotid IMT was an independent predictor of cardiovascular events (P = 0.045). The predictive value for coronary events was similar for carotid IMT and Framingham score as assessed by area under the receiver operating characteristic curves. An improvement in risk prediction was conferred by addition of carotid IMT in a Cox model (global chi(2) increased from 14.1 to 18.1, P = 0.035). CONCLUSIONS: This prospective study confirms that carotid IMT is a marker of cardiovascular risk in this type 2 diabetic cohort, establishes that carotid IMT provides a similar predictive value for coronary events than Framingham score, and suggests that the combination of these two indexes significantly improves risk prediction for these patients.

Pre-PCI angiographic TIMI flow in the culprit coronary artery influences infarct size and microvascular obstruction in STEMI patients.

OBJECTIVE: The influence of initial-thrombolysis in myocardial infarction (i-TIMI) coronary flow in the culprit coronary artery on myocardial infarct and microvascular obstruction (MVO) size is unclear. We assessed the impact on infarct size of i-TIMI flow in the culprit coronary artery, as well as on MVO incidence and size, by contrast-enhanced cardiac magnetic resonance (ce-CMR). METHODS: In a prospective, multicenter study, pre-percutaneous coronary intervention (PCI) coronary occlusion was defined by an i-TIMI flow ≤1, and patency was defined by an i-TIMI flow ≥2. Infarct size, as well as MVO presence and size, were measured on ce-CMR 72h after admission. RESULTS: A total of 140 patients presenting with ST-elevated myocardial infarction referred for primary PCI were included. There was no significant difference in final post-PCI TIMI flow between the groups (2.95±0.02 vs. 2.97±0.02, respectively; p=0.44). In the i-TIMI flow ≤1 group, infarct size was significantly larger (32±17g vs. 21±17g, respectively; p=0.002), MVO was significantly more frequent (74% vs. 53%, respectively; p=0.012), and MVO size was significantly larger [1.3 IQR (0; 7.1) vs. 0 IQR (0; 1.6)], compared to in the i-TIMI ≥2 patient group. CONCLUSION: Initial angiographic TIMI flow in the culprit coronary artery prior to any PCI predicted final infarct size and MVO size: the better was the i-TIMI flow, the smaller were the infarct and MVO size.

Exercising with a denervated heart after cardiac transplantation.

Heart transplantation (HTR) is now an accepted life-extending procedure for those dying of intractable heart failure (CHF). HTR patients expect a high quality of life which implies a reasonable exercise capacity. Nevertheless HTR present unique exercise challenges with both central and peripheral factors of limitation that result in peak oxygen uptakes of 60-70% of age-matched normal subjects. Among central factors persistent chronotropic incompetence questions the occurrence and role of the graft reinnervation. Among peripheral factors the energetic impairement of the skeletal muscle seem to result more from microvascular abnormalities than from an actual deficit in oxidative capacity, questioning the mechanism of recovery from the CHF peripheral myopathy and the role of immunosuppressive drugs. Endurance and resistance training programs may reverse at least in part most but not all of these abnormalities. Training permits patients to engage in sports and even to participate in competitive events that are rewarding to them but also to the community because it promotes organ donation and confidence in medical achievements. Mechanisms of exercise impairments and improvements resulting from training are discussed in the perspective of current literature. Areas of future research and recommendations for the practice of sports after HTR are suggested.

Treatment and prevention of infective endocarditis.

The paper presents the most recent recommendations for the treatment and prevention of infective endocarditis (IE). The treatment of IE is complex and requires close collaboration among specialists in infectious diseases, cardiology, cardiac surgery and microbiology. The mainstay of medical treatment is antibiotic therapy. Theoretical considerations regarding vegetations and antibiotics have practical consequences on the route and modalities of administration of antibiotics and on the techniques used to monitor treatment. The choice of antibiotics depends on the microorganism (streptococci, enterococci, staphylococci, HACEK group [Haemophilus sp., Actinobacillus sp., Cardiobacterium sp., Eikenella sp. and Kingella sp.], Coxiella, Brucella, Legionella, Bartonella, fungi) and on whether IE occurs on native or prosthetic valves. Treatment of IE with negative blood cultures is particularly difficult. Cardiac surgery is often needed during the bacteriologically active period (in ~50% of patients). The decision to intervene and the optimal timing of the intervention requires careful consideration of multiple potential risks: the haemodynamic risk, the infectious risk, the risk due to cardiac lesions, the risk due to extracardiac complications and the risk due to the location of infective endocarditis. Even though the efficacy of antibiotic prophylaxis of IE is not completely proven, it is recommended for selected patients who undergo an at-risk procedure. Lists of cardiac conditions and of medical procedures at risk are presented; specific antibiotic prophylactic regimens for dental and upper respiratory tract procedures in out-patients, procedures under general anaesthesia and urological and GI procedures are outlined.

[Epidemiology of acute coronary syndrome]. / Epidémiologie des syndromes coronaires aigus.

As for myocardial infarction, the epidemiology of acute coronary syndromes is very different according to whether it concerns hospitalized patients only or acute coronary syndromes as a whole: many patients die before any medical intervention. The epidemiology of acute coronary syndromes is not well known since we have almost no specific data regarding unstable angina. The annual incidence of acute coronary syndromes in France is greater than 280 per 100,000 men and 60 per 100,000 women. The 1-month lethality rate is about 50%, increasing sharply with age.