Thrombolysis in myocardial infarction risk score in an observation unit setting.

OBJECTIVE: The Thrombolysis in Myocardial Infarction (TIMI) score is a validated tool for risk stratification of acute coronary syndrome. We hypothesized that the TIMI risk score would be able to risk stratify patients in observation unit for acute coronary syndrome. METHODS: STUDY DESIGN: Retrospective cohort study of consecutive adult patients placed in an urban academic hospital emergency department observation unit with an average annual census of 65,000 between 2004 and 2007. Exclusion criteria included elevated initial cardiac biomarkers, ST segment changes on ECG, unstable vital signs, or unstable arrhythmias. A composite of significant coronary artery disease (CAD) indicators, including diagnosis of myocardial infarction, percutaneous coronary intervention, coronary artery bypass surgery, or death within 30 days and 1 year, were abstracted via chart review and financial record query. The entire cohort was stratified by TIMI risk scores (0-7) and composite event rates with 95% confidence interval were calculated. RESULTS: In total 2228 patients were analyzed. Average age was 54.5 years, 42.0% were male. The overall median TIMI risk score was 1. Eighty (3.6%) patients had 30-day and 119 (5.3%) had 1-year CAD indicators. There was a trend toward increasing rate of composite CAD indicators at 30 days and 1 year with increasing TIMI score, ranging from a 1.2% event rate at 30 days and 1.9% at 1 year for TIMI score of 0 and 12.5% at 30 days and 21.4% at 1 year for TIMI ≥ 4. CONCLUSIONS: In an observation unit cohort, the TIMI risk score is able to risk stratify patients into low-, moderate-, and high-risk groups.

Modulation of I����/I�� by cellular metabolites : implication in the arrhythmogenesis during myocardial ischemia

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Can emerging biomarkers of myocardial remodelling identify asymptomatic hypertensive patients at risk for diastolic dysfunction and diastolic heart failure?

AIMS: Hypertension is one of the main drivers of the heart failure (HF) epidemic. The aims of this study were to profile fibro-inflammatory biomarkers across stages of the hypertensive heart disease (HHD) spectrum and to examine whether particular biochemical profiles in asymptomatic patients identify a higher risk of evolution to HF.

METHODS AND RESULTS: This was a cross-sectional observational study involving a population of 275 stable hypertensive patients divided into two different cohorts: Group 1, asymptomatic hypertension (AH) (n= 94); Group 2, HF with preserved ejection fraction (n= 181). Asymptomatic hypertension patients were further subdivided according to left atrial volume index ≥34 mL/m(2) (n= 30) and <34 mL/m(2) (n= 64). Study assays involved inflammatory markers [interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP1), and tumour necrosis factor α], collagen 1 and 3 metabolic markers [carboxy-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 3 (PIIINP), and carboxy-terminal telopeptide of collagen 1 (CITP)], extra-cellular matrix turnover markers [matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and tissue inhibitor of metalloproteinase 1 (TIMP1)], and the brain natriuretic peptide. Data were adjusted for age, sex, systolic blood pressure, and creatinine. Heart failure with preserved ejection fraction was associated with an increased inflammatory signal (IL6, IL8, and MCP1), an increased fibrotic signal (PIIINP and CITP), and an increased matrix turnover signal (MMP2 and MMP9). Alterations in MMP and TIMP enzymes were found to be significant indicators of greater degrees of asymptomatic left ventricular diastolic dysfunction.

CONCLUSION: These data define varying fibro-inflammatory profiles throughout different stages of HHD. In particular, the observations on MMP9 and TIMP1 raise the possibility of earlier detection of those at risk of evolution to HF which may help focus effective preventative strategies.

Fatigue two months after myocardial infarction may indicate risk for persistent fatigue

Fatigue two months after myocardial infarction may indicate risk for persistent fatigue

Changes of Soluble CD40 Ligand in the Progression of Acute Myocardial Infarction Associate to Endothelial Nitric Oxide Synthase Polymorphisms and Vascular Endothelial Growth Factor But Not to Platelet CD62P Expression

Reported in vitro data implicated soluble CD40 ligand (sCD40L) in endothelial dysfunction and angiogenesis. However, whether sCD40L could exert that influence in endothelial dysfunction and angiogenesis after injury in acute myocardial infarction (AMI) patients remains unclear. In the present study, we evaluated the association of sCD40L with markers of platelet activation, endothelial, and vascular function during a recovery period early after AMI. To achieve this goal, the time changes of soluble, platelet-bound, and microparticle-bound CD40L levels over 1 month were assessed in AMI patients and correlated with endothelial nitric oxide synthase (eNOS) polymorphisms, vascular endothelial growth factor (VEGF) concentrations, and platelet expression of P-selectin (CD62P). The association of soluble form, platelet-bound, and microparticle-bound CD40L with CD62P expression on platelets, a marker of platelet activation, was also assessed to evaluate the role of CD40L in the thrombosis, whereas the association with eNOS and VEGF was to evaluate the role of CD40L in vascular dysfunction. This work shows for the first time that time changes of sCD40L over 1 month after myocardial infarct onset were associated with G894T eNOS polymorphism and with the VEGF concentrations, but not to the platelet CD62P expression. These results indicate that, in terms of AMI pathophysiology, the sCD40L cannot be consider just as being involved in thrombosis and inflammation but also as having a relevant role in vascular and endothelial dysfunction.

Transmyocardial laser revascularization. Personal experience

Background. Indirect revascularization is a therapeutic approach in case of severe angina not suitable for percutaneous or surgical revascularization. Transmyocardial revascularization (TMR) is one of the techniques used for indirect revascularization and it allows to create transmyocardial channels by a laser energy bundle delivered on left ventricular epicardial surface. Benefits of the procedure are related mainly to the angiogenesis caused by inflammation and secondly to the destruction of the nervous fibers of the heart. Patients and method. From September 1996 up to July 1997, 14 patients (9 males – 66.7%, mean age 64.8±7.9 years) underwent TMR. All patients referred angina at rest; Canadian Angina Class was IV in 7 patients (58.3%), III in 5 (41.7%). Before the enrollment, coronarography was routinely performed to find out the feasibility of Coronary Artery Bypass Graft (CABG): 13 patients (91,6%) had coronary arteries lesions not suitable for direct revascularization; this condition was limited only to postero-lateral area in one patient submitted to combined TMR + CABG procedures. Results. Mean discharge time was 3,2±1,3 days after surgery. All patients were discharged in good clinical conditions. Perfusion thallium scintigraphy was performed in 7 patients at a mean follow-up of 4±2 months, showing in all but one an improvement of perfusion defects. Moreover an exercise treadmill improvement was observed in the same patients and all of them are in good clinical conditions, with significantly reduced use of active drugs. Conclusion. Our experience confirms that TMR is a safe and feasible procedure and it offers a therapeutic solution in case of untreatable angina. Moreover, it could be a hybrid approach for patients undergoing CABGs in case of absence of vessels suitable for surgical approach in limited areas of the heart.

Myocardial blood flow quantification by Rb-82 cardiac PET/CT: A detailed reproducibility study between two semi-automatic analysis programs.

BACKGROUND: Several analysis software packages for myocardial blood flow (MBF) quantification from cardiac PET studies exist, but they have not been compared using concordance analysis, which can characterize precision and bias separately. Reproducible measurements are needed for quantification to fully develop its clinical potential. METHODS: Fifty-one patients underwent dynamic Rb-82 PET at rest and during adenosine stress. Data were processed with PMOD and FlowQuant (Lortie model). MBF and myocardial flow reserve (MFR) polar maps were quantified and analyzed using a 17-segment model. Comparisons used Pearson's correlation ρ (measuring precision), Bland and Altman limit-of-agreement and Lin's concordance correlation ρc = ρ·C b (C b measuring systematic bias). RESULTS: Lin's concordance and Pearson's correlation values were very similar, suggesting no systematic bias between software packages with an excellent precision ρ for MBF (ρ = 0.97, ρc = 0.96, C b = 0.99) and good precision for MFR (ρ = 0.83, ρc = 0.76, C b = 0.92). On a per-segment basis, no mean bias was observed on Bland-Altman plots, although PMOD provided slightly higher values than FlowQuant at higher MBF and MFR values (P < .0001). CONCLUSIONS: Concordance between software packages was excellent for MBF and MFR, despite higher values by PMOD at higher MBF values. Both software packages can be used interchangeably for quantification in daily practice of Rb-82 cardiac PET.

Adaptation of the MacNew quality of life questionnaire after myocardial infarction in an Iranian population

BACKGROUND: Health-related quality of life (HRQL) assessment is an important measure of the impact of a wide range of disease process on an individual. To date, no HRQL tool has been evaluated in an Iranian population with cardiovascular disorders, specifically myocardial infarction, a major cause of mortality and morbidity. The MacNew Heart Disease Health-related Quality of Life instrument is a disease-specific HRQL questionnaire with satisfactory validity and reliability when applied cross-culturally. METHOD: A Persian version of MacNew was prepared by both forward and backward translation by bilinguals after which a feasibility test was performed. Consecutive patients (n = 51) admitted to a coronary care unit with acute myocardial infarction were recruited for measurement of their HRQL with retest one month after discharge in the follow-up clinic. Principal components analysis, intra-class correlation reliability, internal consistency, and test-retest reliability were assessed. RESULTS: Trivial rates of missing data confirmed the acceptability of the tool. Principal component analysis revealed that the three domains, emotional, social and physical, performed as well as in the original studies. Internal consistency was high and comparable to other studies, ranging from 0.92 for the emotional and physical domains, to 0.94 for the social domain, and to 0.95 for the Global score. Domain means of 5, 5.3 and 4.9 for emotional, physical and social respectively indicate that our Iranian population has similar emotional and physical but worse social HRQL scores. Test-retest analysis showed significant correlation in emotional and physical domains (P < 0.05). CONCLUSION: The Persian version of the MacNew questionnaire is comparable to the English version. It has high internal consistency and reasonable reproducibility, making it an appropriate specific quality of life tool for population-based studies and clinical practice in Iran in patients who have survived an acute myocardial infraction. Further studies are needed to confirm its validity in larger populations with cardiovascular disease

Improving risk stratification in non-ST-segment elevation myocardial infarction with combined assessment of GRACE and CRUSADE risk scores

BACKGROUND: Risk assessment is fundamental in the management of acute coronary syndromes (ACS), enabling estimation of prognosis. AIMS: To evaluate whether the combined use of GRACE and CRUSADE risk stratification schemes in patients with myocardial infarction outperforms each of the scores individually in terms of mortality and haemorrhagic risk prediction. METHODS: Observational retrospective single-centre cohort study including 566 consecutive patients admitted for non-ST-segment elevation myocardial infarction. The CRUSADE model increased GRACE discriminatory performance in predicting all-cause mortality, ascertained by Cox regression, demonstrating CRUSADE independent and additive predictive value, which was sustained throughout follow-up. The cohort was divided into four different subgroups: G1 (GRACE<141; CRUSADE<41); G2 (GRACE<141; CRUSADE≥41); G3 (GRACE≥141; CRUSADE<41); G4 (GRACE≥141; CRUSADE≥41). RESULTS: Outcomes and variables estimating clinical severity, such as admission Killip-Kimbal class and left ventricular systolic dysfunction, deteriorated progressively throughout the subgroups (G1 to G4). Survival analysis differentiated three risk strata (G1, lowest risk; G2 and G3, intermediate risk; G4, highest risk). The GRACE+CRUSADE model revealed higher prognostic performance (area under the curve [AUC] 0.76) than GRACE alone (AUC 0.70) for mortality prediction, further confirmed by the integrated discrimination improvement index. Moreover, GRACE+CRUSADE combined risk assessment seemed to be valuable in delineating bleeding risk in this setting, identifying G4 as a very high-risk subgroup (hazard ratio 3.5; P<0.001). CONCLUSIONS: Combined risk stratification with GRACE and CRUSADE scores can improve the individual discriminatory power of GRACE and CRUSADE models in the prediction of all-cause mortality and bleeding. This combined assessment is a practical approach that is potentially advantageous in treatment decision-making.

Examination of myocardial electrophysiology using novel panoramic optical mapping techniques

Optical mapping of voltage signals has revolutionised the field and study of cardiac electrophysiology by providing the means to visualise changes in electrical activity at a high temporal and spatial resolution from the cellular to the whole heart level under both normal and disease conditions. The aim of this thesis was to develop a novel method of panoramic optical mapping using a single camera and to study myocardial electrophysiology in isolated Langendorff-perfused rabbit hearts. First, proper procedures for selection, filtering and analysis of the optical data recorded from the panoramic optical mapping system were established. This work was followed by extensive characterisation of the electrical activity across the epicardial surface of the preparation investigating time and heart dependent effects. In an initial study, features of epicardial electrophysiology were examined as the temperature of the heart was reduced below physiological values. This manoeuvre was chosen to mimic the temperatures experienced during various levels of hypothermia in vivo, a condition known to promote arrhythmias. The facility for panoramic optical mapping allowed the extent of changes in conduction timing and pattern of ventricular activation and repolarisation to be assessed. In the main experimental section, changes in epicardial electrical activity were assessed under various pacing conditions in both normal hearts and in a rabbit model of chronic MI. In these experiments, there was significant changes in the pattern of electrical activation corresponding with the changes in pacing regime. These experiments demonstrated a negative correlation between activation time and APD, which was not maintained during ventricular pacing. This suggests that activation pattern is not the sole determinant of action potential duration in intact hearts. Lastly, a realistic 3D computational model of the rabbit left ventricle was developed to simulate the passive and active mechanical properties of the heart. The aim of this model was to infer further information from the experimental optical mapping studies. In future, it would be feasible to gain insight into the electrical and mechanical performance of the heart by simulating experimental pacing conditions in the model.

Impact of Routine Fractional Flow Reserve Evaluation During Coronary Angiography on Management Strategy and Clinical Outcome: One-Year Results of the POST-IT.

Penetration of fractional flow reserve (FFR) in clinical practice varies extensively, and the applicability of results from randomized trials is understudied. We describe the extent to which the information gained from routine FFR affects patient management strategy and clinical outcome. METHODS AND RESULTS: Nonselected patients undergoing coronary angiography, in which at least 1 lesion was interrogated by FFR, were prospectively enrolled in a multicenter registry. FFR-driven change in management strategy (medical therapy, revascularization, or additional stress imaging) was assessed per-lesion and per-patient, and the agreement between final and initial strategies was recorded. Cardiovascular death, myocardial infarction, or unplanned revascularization (MACE) at 1 year was recorded. A total of 1293 lesions were evaluated in 918 patients (mean FFR, 0.81±0.1). Management plan changed in 406 patients (44.2%) and 584 lesions (45.2%). One-year MACE was 6.9%; patients in whom all lesions were deferred had a lower MACE rate (5.3%) than those with at least 1 lesion revascularized (7.3%) or left untreated despite FFR≤0.80 (13.6%; log-rank P=0.014). At the lesion level, deferral of those with an FFR≤0.80 was associated with a 3.1-fold increase in the hazard of cardiovascular death/myocardial infarction/target lesion revascularization (P=0.012). Independent predictors of target lesion revascularization in the deferred lesions were proximal location of the lesion, B2/C type and FFR. CONCLUSIONS: Routine FFR assessment of coronary lesions safely changes management strategy in almost half of the cases. Also, it accurately identifies patients and lesions with a low likelihood of events, in which revascularization can be safely deferred, as opposed to those at high risk when ischemic lesions are left untreated, thus confirming results from randomized trials.

Hydroxychloroquine Myocardial Toxicity in a Patient with Systemic Lupus Erythematosus

Hydroxychloroquine is an antimalarial drug used in many rheumatologic and systemic diseases. Although considered by clinicians to be relatively safe, serious side effects have been documented (retinotoxicity, neuromyotoxicity and cardiotoxicity). We present the case of a 41-year-old woman with systemic lupus erythematosus (SLE) who presented at our institution with acute heart failure after taking hydroxychloroquine for a period of 3 months. An endomyocardial biopsy ruled out myocarditis related to systemic lupus erythematosus but demonstrated pathological changes related to hydroxychloroquine toxicity. It is exceptional to observe such cardiac toxicity after such a low cumulative dose (16 grams). The potential severity and reversibility of this complication underscores the importance of a high level of suspicion and timely diagnosis.

Enhanced engraftment and repairing ability of human adipose-derived stem cells, conveyed by pharmacologically active microcarriers continuously releasing HGF and IGF-1, in healing myocardial infarction in rats

International audience

Simultaneous Acute Pulmonary Embolism and Isolated Septal Myocardial Infarction in a Young Patient

We report here the case of a young patient with a simultaneous isolated septal myocardial infarction (MI) and pulmonary embolism (PE). The aim was to describe a rare clinical entity and to explain why these two pathologies were present at the same time in a young patient.
 A review of literature was established. An interventional cardiologist, an interventional radiologist and a lung specialist were consulted. The diagnostic workup revealed only heterozygous Factor Leiden V mutation. This presentation was probably fortuitous, but worth reporting to our opinion.