Myocarditis or "true" infarction by cardiac magnetic resonance in patients with a clinical diagnosis of myocardial infarction without obstructive coronary disease: A meta-analysis of individual patient data.

OBJECTIVE: Myocardial Infarction with Non-Obstructed Coronary Arteries (MINOCA) is common, but the causes are to a large extent unknown. Thus, we aimed to study the prevalence of myocarditis and "true" myocardial infarction determined by cardiac magnetic resonance (CMR) imaging in MINOCA patients, and risk markers for these two conditions in this population. METHODS: A search was made in the PubMed and Cochrane databases using the search terms "Myocardial infarction", "Coronary angiography", "Normal coronary arteries" and "MRI". All relevant abstracts were read and seven of the studies fulfilled the inclusion criteria; studies describing case series of patients fulfilling the diagnosis of acute myocardial infarction with normal or non-obstructive coronary arteries on coronary angiography that were investigated with CMR imaging. Data from five of these studies are presented. RESULTS: A total of 556 patients from 5 different sites were included. Fifty-one percent were men with a mean age of 52 ± 16 years. Thirty-three per cent of the patients had myocarditis (n = 183), whereas 21% of the patients had infarction on CMR (n = 115). Young age and a high CRP were associated with myocarditis whereas male sex, treated hyperlipidemia, high troponin ratio and low CRP were associated with "true" myocardial infarction. CONCLUSION AND RELEVANCE: The results of this meta-analysis of individual data showed that myocarditis and "true" myocardial infarction are common in MINOCA when determined by CMR imaging. This information emphasizes the importance of performing CMR imaging in MINOCA patients and can be used clinically to guide diagnostics and treatment of MINOCA patients.

Ventilatory thresholds determined from HRV: comparison of 2 methods in obese adolescents.

The development of personalised training programmes is crucial in the management of obesity. We evaluated the ability of 2 heart rate variability analyses to determine ventilatory thresholds (VT) in obese adolescents. 20 adolescents (mean age 14.3±1.6 years and body mass index z-score 4.2±0.1) performed an incremental test to exhaustion before and after a 9-month multidisciplinary management programme. The first (VT1) and second (VT2) ventilatory thresholds were identified by the reference method (gas exchanges). We recorded RR intervals to estimate VT1 and VT2 from heart rate variability using time-domain analysis and time-varying spectral-domain analysis. The coefficient correlations between thresholds were higher with spectral-domain analysis compared to time-domain analysis: Heart rate at VT1: r=0.91 vs. =0.66 and VT2: r=0.91 vs. =0.66; power at VT1: r=0.91 vs. =0.74 and VT2: r=0.93 vs. =0.78; spectral-domain vs. time-domain analysis respectively). No systematic bias in heart rate at VT1 and VT2 with standard deviations <6 bpm were found, confirming that spectral-domain analysis could replace the reference method for the detection of ventilatory thresholds. Furthermore, this technique is sensitive to rehabilitation and re-training, which underlines its utility in clinical practice. This inexpensive and non-invasive tool is promising for prescribing physical activity programs in obese adolescents.

Use of recombinant factor VIIa (NovoSeven(®)) in 8 patients with ongoing life-threatening bleeding treated with fondaparinux.

BACKGROUND: Fondaparinux has a favourable efficacy-safety profile but if major bleeding occurs, reversal of antithrombotic treatment is challenging. We present clinical and biological observations from patients treated with rFVIIa for bleeding under fondaparinux. METHODS: Fondaparinux-treated patients with bleeding (>10% haematocrit decrease) and cardiovascular collapse were eligible. Patients received a single 90 µg/kg bolus rFVIIa. Clinical success was defined as clinical bleeding control without thrombotic complication. A biological criterion of successful antagonization was defined as a >100% increase in peak thrombin generation (C(max)). RESULTS: 8 patients were treated (5 ACS, 3 VTE). Patients received aspirin and clopidogrel (n = 5), eptifibatide (n = 2), fluindione (n = 5). In addition to standard haemostatic methods, all patients received rFVIIa and transfusion. Clinical progression was favourable in 4, with bleeding clinically controlled in <6 h. 1 patient died. Biological success was observed in 4 patients with lowest baseline anti-Xa (0.67-0.92 U/L); ¾ had clinical success. In patients with baseline anti-Xa >1.0 U/L (1.14-1.62 U/L), increase in C(max) was low; ¾ had no clinical bleeding control. CONCLUSION: This series is the largest describing rFVIIa use to control bleeding in patients under fondaparinux. rVFIIa was considered efficient in 50%, suggesting inefficacy in the context of elevated anti-Xa.

Predictive value of admission hyperglycaemia on mortality in patients with acute myocardial infarction.

RATIONALE AND AIM: In patients with an acute myocardial infarction, admission hyperglycaemia (AH) is a major risk factor for mortality. However, the predictive value of AH, when the risk score and use of guidelines-recommended treatments are considered, is poorly documented. METHODS: The first fasting plasma glucose levels after admission, risk level, guidelines-recommended treatment use and 1-year mortality were recorded. Patients with first fasting glucose level after admission > 7.7 mmo/l were considered to have AH. RESULTS: Three hundred and twenty patients with ST segment elevation myocardial infarction (STEMI) and 404 with non-ST segment elevation myocardial infarction (NSTEMI) were included. One hundred and seventy-five (24%) patients had pre-existing diabetes (diabetes group), 154 (21%) had AH (AH+ group) and the remainding 395 (55%) had neither diabetes nor AH (AH- group). The Global Registry of Acute Coronary Events (GRACE) risk score was lower in the AH- group, but the use of guidelines-recommended treatment was comparable in all groups. At 1 year, the mortality rate was higher in the AH+ group compared with the AH- group (18.8 vs. 6.1%, P < 0.01) and similar to that in the diabetes group (18.8 vs. 16.6%, P = NS). The relation between glycaemic status and mortality remained strong [AH+ vs. AH-, OR = 3.0 (1.5, 6.0) and diabetes vs. AH-, OR = 3.6 (1.7, 6.6)] after adjustment for the GRACE risk score [OR = 2.4 (1.8, 3.1) per 10% increase] and for treatment score [OR = 0.7 (0.6, 0.8) per 10% increase]. CONCLUSIONS: In patients without a history of diabetes, the presence of AH indicates an increased risk of 1-year mortality, similar to that of patients with diabetes, even when the risk score and use of guidelines-recommended treatment are controlled for.

[When to suspect pulmonary embolism in a patient with deep venous thrombosis?]. / Quand suspecter une embolie pulmonaire chez un malade ayant une thrombose veineuse profonde?

The approach to take in trying to establish or disprove a diagnosis of pulmonary embolism in the presence of deep vein thrombosis is the subject of some controversy nowadays. Systematic perfusion lung scan can be proposed, given the mediocre specificity of the clinical symptoms of embolism or the high frequency of asymptomatic pulmonary embolism. This strategy, however, is not validated in terms of cost-efficacy. In practical terms, favourable evolution and the low rate of recurrent embolism observed with a well executed anticoagulant treatment pleads against systematic scintigraphy. Because of its moderate sensitivity, systematic echocardiography probably should not be an element of the assessment of asymptomatic pulmonary embolism. The advent of spiral CT scan in the management of such patients could however make it necessary to reconsider this position, by allowing complete venous and pulmonary examination in thrombo-embolic disease.

Use of dobutamine stress echocardiography in detecting silent myocardial ischaemia in asymptomatic diabetic patients: a comparison with thallium scintigraphy and exercise testing.

AIMS: Silent myocardial ischaemia is frequent in diabetic patients. The aim of this study was to compare the efficacy of thallium-201 single-photon emission computed tomography (201Tl SPECT) coupled with exercise stress testing (EST), and dobutamine stress echocardiography (DSE) in the detection of asymptomatic coronary artery disease. METHODS: Fifty-six asymptomatic diabetic patients, with a known duration of diabetes > 15 years for Type 1 and > 5 years for Type 2, having at least three added risk factors, but without rest ECG abnormalities, were enrolled in this prospective study. All of them were submitted to DSE with a maximum infusion rate of 40 microg/kg per min dobutamine +/- i.v. atropine, and to 201Tl SPECT coupled with EST. Coronary angiography was performed if at least one test was abnormal. RESULTS: Diabetic patients were 37 males and 19 females, aged mean (sd) 60 +/- 10 years, 10 Type 1 and 46 Type 2, with a known duration of disease of mean (sd) 17 +/- 9 years. Feasibility of DSE was 91%. No serious complication occurred during the test. Coronary angiography was performed in 26 patients (47%); 17 were abnormal (30% of the whole group): six patients had a one-vessel, six a two-vessel and five a three-vessel disease. Predictive positive value was 69% for DSE, 75% for 201Tl SPECT and 60% for EST. DSE was falsely negative in four cases vs. eight for 201Tl SPECT and nine for EST. CONCLUSIONS: Asymptomatic coronary disease is common in diabetes associated with other risk factors. DSE appears useful in its detection and a good alternative to 201Tl SPECT.

False lumen patency as a predictor of late outcome in aortic dissection.

Aortic dissection (AD) is a disease with a high-risk of mortality. Late deaths are often related to complications in nonoperated aortic segments. Between 1984 and 1996, we retrospectively analyzed the data of 109 patients with acute AD (81 men and 28 women; average age 61 +/- 14 years). All imaging examinations were reviewed, and a magnetic resonance imaging examination was performed at the time of the study. Aortic diameters were measured on each aortic segment. Predictive factors of mortality were determined by Cox's proportional hazard model, in univariate and multivariate analyses, using BMDP statistical software. Follow-up was an average of 44 +/- 46 months (range 24 to 164). Actuarial survival rates were 52%, 46%, and 37% at 1, 5, and 10 years, respectively, for type A AD versus 76%, 72%, and 46% for type B AD. Predictors of late mortality were age >70 years and postoperative false lumen patency of the thoracic descending aorta (RR 3.4, 95% confidence intervals 1.20 to 9.8). Descending aorta diameter was larger when false lumen was patent (31 vs 44 mm; p = 0.02) in type A AD. Furthermore, patency was less frequent in operated type A AD when surgery had been extended to the aortic arch. Thus, patency of descending aorta false lumen is responsible for progressive aortic dilation. In type A AD, open distal repair makes it possible to check the aortic arch and replace it when necessary, decreases the false lumen patency rate, and improves late survival.

Lack of agreement between left ventricular volumes and ejection fraction determined by two-dimensional echocardiography and contrast cineangiography in postinfarction patients.

OBJECTIVE: To assess the agreement between left ventricular (LV) volumes and ejection fraction (EF) determined by two-dimensional echocardiography (2-D echo) and by cineangiography in postinfarction patients. DESIGN: LV end-diastolic and end-systolic volumes indexed (EDVI and ESVI) to body surface area as well as EF were determined by both methods in all patients. SETTING: Multicenter trial conducted in five university hospitals. PATIENTS: 63 patients, 61 male, two female, mean age 55.5 +/- 10.4 years, suffering from a recent myocardial infarction. Eighty-one pairs of measurements were available. METHODS: The results of biplane 2-D echo measures, using apical four-chamber (4C) and two-chamber (2C) views were compared to those of a 30 degrees right anterior oblique cineangiography projection, using either the apical method of discs or the area-length 2-D echo method. Moreover, eyeball EF was estimated at 2-D echo and cineangiography, and was compared to the conventional methods. The agreement between results was assessed by the Bland and Altman method. RESULTS: The agreement between 2-D echo and cineangiography results was poor. Mean differences (MD) were -21.8 (EDVI, ml/m(2)), -9.5 (ESVI, ml/m(2)), and -0.9 (EF, %), respectively for 2-D echo method of discs versus cineangiography, and -23.2, -9.3, and -5.7 for area-length 2-D echo versus cineangiography. For EF (%), MD was -3.6 for eyeball cineangiography versus cineangiography, -1.3 for eyeball 2-D echo versus method of discs, and +0.30 for eyeball 2-D echo versus area-length 2-D echo, respectively. Two-dimensional echo is likely to underestimate LV volumes compared to cineangiography, especially for largest volumes. Even for EF, discrepancies are large, with a lack of agreement of 21%-25% between conventional methods, but agreement is better between eyeball EF and usual methods. CONCLUSIONS: Even with modern echocardiographic devices, agreement between 2-D echo and cineangiography-derived LV volumes and EF remains moderate, and both methods must not be considered interchangeable in clinical practice.

Cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori IgG antibodies and restenosis after stent implantation: an angiographic and intravascular ultrasound study.

OBJECTIVE: To determine the impact of previous infection with cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori on neointimal proliferation after coronary angioplasty with stent implantation. DESIGN: The study population was made up of 180 patients who had stent implantation in a native coronary artery with systematic angiographic and intravascular ultrasound (IVUS) follow up at six months. Quantitative coronary angiography was used to assess the late lumen loss. The mean area of neointimal tissue within the stent and the ratio of neointimal tissue to stent area were assessed from IVUS images. Previous cytomegalovirus, C pneumoniae, and H pylori infection was identified by IgG antibody determination. RESULTS: Previous cytomegalovirus infection was detected in 50% of the population, previous C pneumoniae in 18%, and previous H pylori in 33%. Mean (SD) reference diameter was 2.94 (0.48) mm and mean minimum lumen diameter after stent implantation was 2.45 (0.42) mm. At six months, the mean late loss was 0.74 (0.50) mm, the mean neointimal tissue area was 3.8 (1.7) mm(2), and the average ratio of neointimal tissue area to stent area was 45 (18)%. None of these variables of restenosis was linked to any of the three infectious agents. By multivariate analysis, lesion length was the variable best correlated with mean neointimal tissue area, the ratio of neointimal tissue to stent area, and late loss, explaining respectively 31%, 39%, and 8% of their variability. CONCLUSIONS: Previous infection with cytomegalovirus, C pneumoniae, or H pylori was not a contributing factor in the process of restenosis after stent implantation.

Gene delivery from a DNA controlled-release stent in porcine coronary arteries.

Expandable intra-arterial stents are widely used for treating coronary disease. We hypothesized that local gene delivery could be achieved with the controlled release of DNA from a polymer coating on an expandable stent. Our paper reports the first successful transfection in vivo using a DNA controlled-release stent. Green fluorescent protein (GFP) plasmid DNA within emulsion-coated stents was efficiently expressed in cell cultures (7.9% +/- 0.7% vs. 0.6% +/- 0.2% control, p < 0.001) of rat aortic smooth muscle cells. In a series of pig stent-angioplasty studies, GFP expression was observed in all coronary arteries (normal, nondiseased) in the DNA-treated group, but not in control arteries. GFP plasmid DNA in the arterial wall was confirmed by PCR, and GFP presence in the pig coronaries was confirmed by immunohistochemistry. Thus, DNA-eluting stents are capable of arterial transfection, and could be useful as delivery systems for candidate vectors for gene therapy of cardiovascular diseases.

Local delivery of nadroparin for the prevention of neointimal hyperplasia following stent implantation: results of the IMPRESS trial. A multicentre, randomized, clinical, angiographic and intravascular ultrasound study.

BACKGROUND: We hypothesized that intramural delivery of nadroparin, a low molecular weight heparin, would prevent in-stent restenosis by inhibiting neointimal hyperplasia in an angioplasty model free of arterial remodelling. METHODS AND RESULTS: In a prospective randomized multicentre trial, 250 patients submitted to balloon angioplasty followed by stent implantation were randomized into control group (no local drug delivery) or intramural delivery of nadroparin (2 ml of 2500 anti-Xa-units/ml with a microporous catheter). An ancillary intravascular ultrasound substudy was performed to supplement angiographic data with specific measurements of in-stent neointimal hyperplasia. The primary end-point was the late loss in minimal luminal diameter on the 6 month follow-up angiogram. Secondary end-points included feasibility and safety of local nadroparin delivery, and major adverse cardiac events at 8 weeks and 6 months follow-up. Local delivery of nadroparin was successful in 124 patients (99.2% success rate) and was not associated with an increase in stent thrombosis, coronary artery dissection, side branch occlusion, distal embolization or abrupt arterial closure. At angiographic follow-up, the late loss in lumen diameter was 0.84 +/- 0.62 mm in the control group compared to 0.88 +/- 0.63 mm in the nadroparin group (P=0.56). Angiographic restenosis rate (defined as a >50% diameter stenosis) did not differ in the control group (20%) compared to the nadroparin group (24%). The average area of neointimal tissue within the stent was 2.86 +/- 0.64 mm(2) vs 2.90 +/- 0.53 mm(2) (P=0.57), control vs nadroparin groups. There was no difference in major adverse cardiac events at any time (88.8% vs 89.6% event free survival at 6 months, control vs nadroparin). CONCLUSION: Intramural delivery of nadroparin with a microporous catheter after stent deployment was feasible and safe but had no effect in reducing restenosis or the occurrence of major adverse clinical events over 6 months.

Predictors of clinical outcome following percutaneous intervention for in-stent restenosis.

Percutaneous intervention for the first episode of in-stent restenosis was performed in 177 patients 5.4 +/- 0.3 months after native coronary stent implantation. Medical records were reviewed and patients contacted 13.3 +/- 1.2 months after in-stent intervention to ascertain the subsequent clinical course. The effects of demographic, procedural, and angiographic variables on clinical outcomes were determined. At 2 years, Kaplan-Meier estimated survival was 93 +/- 3% and freedom from death, myocardial infarction, and a third target artery revascularization (TAR) was 67 +/- 4%. The actuarial frequency of a third TAR was 26 +/- 4% at 1 year. Stratification of outcomes according to timing of in-stent intervention revealed an approximate twofold higher frequency of adverse events among patients with early (