Antithrombotic therapy management in a man with ST elevation myocardial infarction and triple positive antiphospholipid syndrome: case report and literature review.

OBJECTIVE: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder associated with vascular complications including acute myocardial infarction (AMI). AMI pathogenesis in APS is considered to be acute thrombosis of coronary arteries, in contrast to typical AMI where the pathogenesis is atherosclerotic plaque rupture. Therapeutic management is therefore a clinical challenge. There is no consensus among experts about optimal antithrombotic therapy in secondary prevention. The role of coronary stents is still to be determined, due to the higher rates of stent thrombosis after percutaneous coronary intervention (PCI) in APS patients. CASE REPORT: We described the case of a 51-year-old male, smoker, that presented with anterior ST elevation myocardial infarction (STEMI) as first manifestation of APS. The patient underwent primary PCI on left main and ostial left anterior descending artery. RESULTS: We discussed antithrombotic therapy management after PCI in our patient and reviewed literature on current therapeutic management of this specific population. CONCLUSIONS: APS patients with STEMI should undergo PCI, usually associated with thrombus aspiration, and in select cases stent implantation in the culprit lesion. In the latter case, triple antithrombotic therapy with short-term dual antiplatelet therapy and long-term anticoagulant therapy is recommended. Clinicians should include autoimmune etiologies in the differential diagnosis of underlying causes of AMI.

Takotsubo cardiomyopathy and flecainide toxicity: a case report and brief literature review.

OBJECTIVE: Takotsubo syndrome, also known as stress cardiomyopathy, is predominantly reported in postmenopausal women and it is often triggered by a physical or emotional stressor. CASE REPORT: We present the case of a 44-year-old Caucasian woman admitted to the emergency department after voluntary intake of 20 tablets of flecainide 150 mg to commit suicide. During the in-hospital stay in the Cardiac Intensive Care Unit, the patient developed Takotsubo syndrome. CONCLUSIONS: The relative role of flecainide as a possible trigger of the syndrome is discussed in the context of the current literature evidence.

Increase of renal resistive index and mineral metabolism disorder in patients with acute coronary syndrome with preserved renal function.

OBJECTIVE: Coronary artery disease is one of the first causes of death in the Western world; for this reason, it is essential to identify new, systemic, non-invasive and low-cost cardiovascular risk markers. The acute coronary syndrome includes ST-Elevation Myocardial Infarction (STEMI) and Non-ST-Elevation Myocardial Infarction (NSTEMI), based on ECG findings. We aimed to evaluate Renal Resistive Index (RRI) as a marker of cardiovascular risk and assess the associations with other cardiovascular risk factors (metabolic indexes, mineral metabolism disorders and endothelial dysfunction and atherosclerosis markers) in STEMI and NSTEMI patients. PATIENTS AND METHODS: Clinical, laboratory and instrumental examinations as metabolic and inflammation indexes, markers of atherosclerosis and endothelial dysfunction (renal function, mineral metabolism disorders, inflammation indexes, Intima Media Thickness (IMT), Ankle Brachial Pressure Index, Left Ventricular Mass Index, Relative Wall Thickness) were performed. RESULTS: Eighty-one patients with STEMI and NSTEMI were enrolled. We showed a significant positive correlation between RRI and age (p<0.01), intact parathyroid hormone (p<0.01) and IMT (p<0.01), as well as a significant negative correlation between RRI and body surface area (BSA) (p=0.02), estimated Glomerular Filtration Rate (eGFR) (p<0.01), serum calcium (p<0.01) and 25-hydroxy-vitamin D (p=0.03). Moreover, we found a significant correlation between RRI and male patients (p<0.01), coronary artery disease history (CAD) (p=0.049), hypertension (p=0.025) and left ventricular eccentric hypertrophy (LVEH) (p=0.047). CONCLUSIONS: Our study showed an association between RRI and the main traditional and non-traditional cardiovascular risk factors involved in atherosclerosis pathogenesis, such as age, BSA, hypertension, male sex, CAD history, mineral metabolism disorders and LVEH, in patients with preserved renal function. Moreover, we found a significant correlation between RRI and eGFR, suggesting that RRI could be useful in the evaluation of both renal function and progression of renal damage, even in an early stage with a conserved or only slightly reduced kidney function. We also showed a significant correlation with some markers of systemic atherosclerosis such as IMT and LVEH. For a more precise assessment of prognosis and cardiovascular risk in patients with high cardiovascular mortality, we suggest performing a systematic RRI evaluation, considering the non-invasive nature of the procedure, its reproducibility, easy execution, and low costs.

Meta-analysis of the impact on early and late mortality of TAVI compared to surgical aortic valve replacement in high and low-intermediate surgical risk patients.

OBJECTIVE: We studied the impact of transcatheter aortic valve implantation (TAVI) compared to the surgical aortic valve replacement (SAVR) on 30-day and one-year mortality from randomized controlled trials (RCTs) in patients with severe aortic stenosis at high or low-intermediate surgical risk. MATERIALS AND METHODS: All RCTs were retrieved through PubMed computerized database and the site https://www.clinicaltrials.gov from January 2010 until March 31st, 2019. The absolute risk reduction (RD) with the 95% confidence interval (CI) was used to assess the effectiveness of the intervention under comparison. We evaluated overall mortality rates at 30-day and one-year follow-up in the comparison between TAVI vs. SAVR. We also evaluated the role played by the site access for TAVI performed through the femoral or subclavian artery (TV-TAVI) vs. SAVR, or transapically (TA-TAVI) vs. SAVR. RESULTS: In the "as-treated population" the overall 30-day mortality was significantly lower in TAVI (p=0.03) with respect to SAVR. However, the analysis for TAVI subgroups showed that 30-day mortality was (1) significantly lower in TV-TAVI vs. SAVR (p=0.006), (2) increased, not significantly, in TA-TAVI vs. SAVR (p=0.62). No significant differences were found between TAVI vs. SAVR at one-year follow-up. CONCLUSIONS: The results of our meta-analysis suggest that TV-TAVI is a powerful tool in the treatment of severe aortic stenosis at high or low-intermediate surgical risk, with a significant lower mortality with respect to SAVR. On the contrary, SAVR seems to provide better results than TA-TAVI.

The Oxidative Stress-Induced miR-200c Is Upregulated in Psoriasis and Correlates with Disease Severity and Determinants of Cardiovascular Risk.

Psoriasis is a chronic inflammatory skin disease associated with reactive oxygen species (ROS) increase and a higher risk of cardiovascular (CV) events. We previously showed that the miR-200 family (miR-200s) is induced by ROS, miR-200c being the most upregulated member responsible for apoptosis, senescence, ROS increase, and nitric oxide decrease, finally causing endothelial dysfunction. Moreover, circulating miR-200c increases in familial hypercholesterolemic children and in plaques and plasma of atherosclerotic patients, two pathologies associated with increased ROS. Given miR-200s' role in endothelial dysfunction, ROS, and inflammation, we hypothesized that miR-200s were modulated in lesional skin (LS) and plasma of psoriatic patients (Pso) and that their levels correlated with some CV risk determinants at a subclinical level. All Pso had severe psoriasis, i.e., Psoriasis Area and Severity Index (PASI) > 10, and one of the following: at least two systemic psoriasis treatments, age at onset < 40 years, and disease duration > 10 years. RNA was extracted from plasma (Pso, N = 29; Ctrl, N = 29) and from nonlesional skin (NLS) and LS of 6 Pso and 6 healthy subject skin (HS) biopsies. miR-200 levels were assayed by quantitative RT-PCR. We found that all miR-200s were increased in LS vs. NLS and miR-200c was the most expressed and upregulated in LS vs. HS. In addition, circulating miR-200c and miR-200a were upregulated in Pso vs. Ctrl. Further, miR-200c positively correlated with PASI, disease duration, left ventricular (LV) mass, LV relative wall thickness (RWT), and E/e', a marker of diastolic dysfunction. Multiple regression analysis indicates a direct association between miR-200c and both RWT and LV mass. Circulating miR-200a correlated positively only with LV mass and arterial pressure augmentation index, a measure of stiffness, although the correlations were nearly significant (P = 0.06). In conclusion, miR-200c is upregulated in LS and plasma of Pso, suggesting its role in ROS increase and inflammation associated with CV risk in psoriasis.

The natural history of prehypertension. A 20-year follow-up.

OBJECTIVE: According to the JNC7 report, prehypertension category includes subjects with systolic blood pressure between 120 and 139 mmHg and/or diastolic blood pressure between 80 and 89 mmHg that would be at risk for developing hypertension and its untoward sequelae as myocardial infarction and cerebrovascular disease. Moreover, ambulatory blood pressure monitoring made it possible to detect subjects with masked hypertension, who are at risk of greater target organ damage than those with normal ambulatory or home blood pressure. The aim of this study was to evaluate the risk of cardiac, cerebral and vascular events in a group of prehypertensive subjects, with and without masked hypertension. PATIENTS AND METHODS: We studied 204 consecutive asymptomatic prehypertensive subjects without history and signs of cardiovascular disease or diabetes. All the subjects underwent clinical evaluation, electrocardiogram, routine laboratory tests and ambulatory blood pressure monitoring. They were followed-up for a maximum of 237 months or until a cardiovascular event occurred. RESULTS: Twenty-seven cardiovascular events (13.2%) occurred, including 4 abdominal aortic aneurysms. Age (p<0.0001), total cholesterol (p=0.004), smoking (p=0.03) and clinically overt hypertension development (p=0.011) were related to cardiovascular events. Prognosis was not related to masked hypertension. CONCLUSIONS: The results of this study suggest that, in subjects with prehypertension, followed for 20 years, traditional cardiovascular risk factors and development of clinically overt hypertension could be more relevant than ambulatory hypertension in the prediction of an adverse outcome.

Is it possible a new definition of metabolic syndrome in childhood?

OBJECTIVE: To investigate whether a group of Italian children and adolescents who were diagnosed to have metabolic syndrome (MS) according to a new ethnic age and gender specific definition had, in comparison with a control group, other signs and metabolic risk factors which are commonly associated with MS. PATIENTS AND METHODS: The cross-sectional study population included 300 subjects (51% boys, age range 6-14 years), who were divided into 2 groups according to the presence of MS, diagnosed on the basis of 3/5 factors derived from the age and gender specific quantile distribution of MS components in a large regional Italian population survey (Calabrian Sierras Community Study, CSCS). In all subjects the following data were collected: anthropometric measures, blood pressure, liver function, C-reactive protein (hsCRP), uric acid blood levels, lipid and glucose profile. Triglycerides/HDL-cholesterol (TG/HDL-C) ratio was calculated. RESULTS: There were 38 subjects (13%) with MS, who had higher indices of growth and fat distribution and higher blood levels of uric acid, alanine aminotransferase and gamma-glutamyltransferase. TG/HDL ratio was higher (median 3.11 vs. 1.14, p = 0.00001) in MS subjects who had lower apolipoprotein A and higher apolipoprotein B and non-HDL-C levels. hsCRP was not different between groups. CONCLUSIONS: Our ethnic age and gender specific definition of MS in Italian children and adolescents was able to identify in a youth group different cardiometabolic risk factors related to insulin resistance, endothelial damage and nonalcoholic fatty liver disease, which are commonly associated with MS diagnosis.

Evaluation of hand circulation with CardioWaves photoplethysmograph device during Allen test in healthy volunteers.

OBJECTIVE: Radial artery occlusion is a potential complication of transradial procedures and its occurrence ranges from 0.8 to 30%. It is virtually always asymptomatic but the functional and sensorial consequences of a long acting hand hypoperfusion could go underestimated. CardioWaves is a novel photoplethysmograh device that allows us to detect the pulse wave amplitude of the blood flowing to the hand. Our objective was to assess in normal subjects the hand blood flow supplied by radial arteries and ulnopalmar arches, respectively, by using CardioWaves device during modified Allen's test (MAT). PATIENTS AND METHODS: MAT was performed on both hands of 60 normal subjects, age ranging 21 to 66 years, without any cardiovascular factor risk. RESULTS: Photoplethysmograh and MAT showed a high positive linear correlation (r=0.93). Despite that, MAT tends to give a higher reading by between 1.05 and 1.6 sec. 11 of 120 readings (9%) by CardioWaves showed values of radial/ulnar pulse amplitude ratio more than mean + 1 SD, suggesting a significant decrease in ulnopalmar arterial circulation when radial blood flow supply would ceased. CONCLUSIONS: The CardioWaves device allows us an accurate reading of the flow because of its independency from respiratory changes. Furthemore, the evaluation of radial and ulnar pulse wave amplitude and the ratio between them would reveal an insufficient blood flow supply by the ulnar artery irrespective of the MAT results. We suggest that their assessment before performing coronary angiography and interventions may reduce potential complication of transradial access.

Long-term results of a randomized controlled trial analyzing the role of systematic pre-operative coronary angiography before elective carotid endarterectomy in patients with asymptomatic coronary artery disease.

OBJECTIVES: To evaluate the potential benefit of systematic preoperative coronary-artery angiography followed by selective coronary-artery revascularization on the incidence of myocardial infarction (MI) in patients undergoing carotid endarterectomy (CEA) without a previous history of coronary artery disease (CAD). METHODS: We randomised 426 patients who were candidates for CEA, with no history of CAD, a normal electrocardiogram (ECG), and a normal cardiac ultrasound. In group A (n = 216) all patients underwent coronary angiography before CEA. In group B (n = 210) CEA was performed without coronary angiography. Patients were not blinded for relevant assessments during follow-up. Primary end-point was the occurrence of MI at 3.5 years. The secondary end-point was the overall survival rate. Median length of follow-up was 6.2 years. RESULTS: In group A, coronary angiography revealed significant coronary artery stenosis in 68 patients (31.5%). Among them, 66 underwent percutaneous Intervention (PCI) prior to CEA and 2 received combined CEA and coronary-artery bypass grafting (CABG). Postoperatively, no MI was observed in group A, whereas 6 MI occurred in group B, one of which was fatal (p = .01). During the study period, 3 MI occurred in group A (1.4%) and 33 were observed in group B (15.7%), 6 of which were fatal. The Cox model demonstrated a reduced risk of MI for patients in group A receiving coronary angiography (HR,.078; 95% CI, 0.024-0.256; p < .001). In addition, patients with diabetes and patients <70 years presented with an increased risk of MI. Survival analysis at 6 years by Kaplan-Meier estimates was 95.6 ± 3.2% in Group A and 89.7 ± 3.7% in group B (Log Rank = 6.54, p = .01). CONCLUSIONS: In asymptomatic coronary-artery patients, systematic coronary angiography prior to CEA followed by selective PCI or CABG significantly reduces the incidence of late MI and increases long-term survival. (ClinicalTrials.gov number, NCT02260453).

Diagnostic accuracy of 320-row computed tomography as compared with invasive coronary angiography in unselected, consecutive patients with suspected coronary artery disease.

Noninvasive coronary angiography with multislice computed tomography (CT) scanners is feasible with high sensitivity and negative predictive value. The radiation exposure associated with this technique, however, is high and concerns in the widespread use of CT have arisen. We evaluated the diagnostic accuracy of coronary angiography using 320-row CT, which avoids exposure-intensive overscanning and overranging. We prospectively studied 118 unselected consecutive patients with suspected coronary artery disease (CAD) referred for invasive coronary angiography (ICA). All patients had 320-row CT within 1 week of ICA, which, together with quantitative analysis, served as the reference standard. Of the 65 out of 118 patients who were diagnosed as having CAD by ICA, 64 (98 %) were correctly identified at 320-row CT. Noteworthy, 320-row CT correctly detected CAD in 3 patients with atrial fibrillation and ruled out the disease in the other 8 patients. From 151 significant coronary stenoses detected on ICA, 137 (91 %) were correctly identified with 320-row CT. In the per-patient analysis, sensitivity and specificity of 320-row CT were 98 and 91 %, respectively. In the per-vessel analysis, sensitivity and specificity of 320-row CT were 93 and 95 %, respectively. In the per segment analysis, sensitivity and specificity of 320-row CT were 91 and 99 %, respectively. Diameter stenosis determined with the use of CT showed good correlation with ICA (P < 0.001, R = 0.81) without significant underestimation or overestimation (-3.1 ± 24.4 %; P = 0.08). Comparison of CT with ICA revealed a significantly smaller effective radiation dose (3.1 ± 2.3 vs. 6.5 ± 4.2 mSv; P < 0.05) and amount of contrast agent required (99 ± 51 vs. 65 ± 42 ml, P < 0.05) for 320 row CT. The present study in an unselected population including patients with atrial fibrillation demonstrates that 320-row CT may significantly reduce the radiation dose and amount of contrast agent required compared with ICA while maintaining a very high diagnostic accuracy.

ECHO and magnetic resonance imaging in a patient with high bleeding risk and ventricular perforation: a case report and literature review.

Myocardial perforation is a complication following pacemaker implantation that may cause cardiac tamponade. We present an original case of myocardial lead perforation not complicated by acute cardiac tamponade. The patient with an acute myocardial infarct had a high bleeding risk both in the acute phase of lead insertion (anticoagulant and triple platelet anti-aggregation therapy) and after few days, the percutaneous extraction lead for the double platelet antiaggregant therapy. Torrent-Guasp's theory is considered for explaining the clinical course of patient. Echocardiography and magnetic resonance imaging (MRI) evaluation showed a diffuse pericardial non-hemorrhagic fibrinous effusion and guide the clinical management.

Systematic preoperative coronary angiography and stenting improves postoperative results of carotid endarterectomy in patients with asymptomatic coronary artery disease: a randomised controlled trial.

OBJECTIVE: To evaluate the usefulness of systematic coronary angiography followed, if needed, by coronary artery angioplasty (percutaneous coronary intervention (PCI)) on the incidence of cardiac ischaemic events after carotid endarterectomy (CEA) in patients without evidence of coronary artery disease (CAD). MATERIALS AND METHODS: From January 2005 to December 2008, 426 patients, candidates for CEA, with no history of CAD and with normal cardiac ultrasound and electrocardiography (ECG), were randomised into two groups. In group A (n=216) all the patients had coronary angiography performed before CEA. In group B, all the patients had CEA without previous coronary angiography. In group A, 66 patients presenting significant coronary artery lesions at angiography received PCI before CEA. They subsequently underwent surgery under aspirin (100 mg day(-1)) and clopidogrel (75 mg day(-1)). CEA was performed within a median delay of 4 days after PCI (range: 1-8 days). Risk factors, indications for CEA and surgical techniques were comparable in both groups (p>0.05). The primary combined endpoint of the study was the incidence of postoperative myocardial ischaemic events combined with the incidence of complications of coronary angiography. Secondary endpoints were death and stroke rates after CEA and incidence of cervical haematoma. RESULTS: Postoperative mortality was 0% in group A and 0.9% in group B (p=0.24). One postoperative stroke (0.5%) occurred in group A, and two (0.9%) in group B (p=0.62). No postoperative myocardial event was observed in group A, whereas nine ischaemic events were observed in group B, including one fatal myocardial infarction (p=0.01). Binary logistic regression analysis demonstrated that preoperative coronary angiography was the only independent variable that predicted the occurrence of postoperative coronary ischaemia after CEA. The odds ratio for coronary angiography (group A) indicated that when holding all other variables constant, a patient having preoperative coronary angiography before carotid surgery was 4 times less likely to have a cardiac ischaemic event after carotid surgery. No complications related to coronary angiography were observed and no cervical haematomas occurred in patients undergoing surgery under aspirin and clopidogrel in this study. CONCLUSIONS: Systematic preoperative coronary angiography, possibly followed by PCI, significantly reduces the incidence of postoperative myocardial events after CEA in patients without clinical evidence of CAD.

Antitissue transglutaminase antibodies in acute coronary syndrome: an alert signal of myocardial tissue lesion?

BACKGROUND AND AIM: Antitransglutaminase, previously considered identical to antiendomysial in coeliac sprue (CS), have been reported in end-stage heart failure. To clarify the above-mentioned data, we evaluated these antibodies in a cohort of cardiological patients with respect to troponin I, creatine kinase (CK), MB fraction creatine kinase (CK-MB mass) and myoglobin. METHODS: Forty-one patients with acute coronary syndrome (ACS), 39 with dilated cardiomyopathy (DCM), 45 with CS and 58 blood donors (BDs) were evaluated. Antitransglutaminase and antiendomysial antibodies were tested in serum of the patients being studied. RESULTS: High-positive antitransglutaminase values were found in CS, whilst low-positive values were also found in ACS and DCM. In patients at the second ACS, antibody levels were higher than in those at the first cardiac event. In patients with infarct Q, antitransglutaminase were higher than those in infarct non-Q, in which antibody levels were higher than those in unstable angina. A correlation between antitransglutaminase and troponin I, CK, CK-MB mass and myoglobin was found. Finally, antibody levels rose to reach a peak at 30 days from the cardiac event, whereas after further 150 days, approached the values of BDs. Antiendomysial were detectable only in CS. CONCLUSIONS: Data highlight that antitransglutaminase can occur in cardiological patients, and that these antibodies are related to the severity/extent of the myocardial tissue lesion. This feature suggests a loss of specificity for antitransglutaminase in CS. Furthermore, the possibility of employing these antibodies in the long-term follow-up of ACS, could become an object of interesting discussion.

Detection of coronary artery stenoses using breath-hold magnetic resonance coronary angiography. Comparison with conventional x-ray angiography.

PURPOSE: To detect coronary artery stenoses, we compare breath-hold magnetic resonance coronary angiography (MRCA) to conventional coronary angiography (CA). MATERIALS AND METHODS: Sixty-five patients with suspected coronary artery disease underwent MRCA and CA within one week. MRCA examination was performed by using the two-dimensional (2D) breath-hold technique with a fast spoil gradient-echo sequence/spiral. Each imaging sequence was obtained within one breath-hold in expiration (14 seconds of apnoea). The assessment of coronary artery stenoses on magnetic resonance (MR) angiograms was independently performed by two blinded readers and compared to conventional CA images. RESULTS: Three hundred and ninety segments were evaluated by the two imaging techniques. MRCA correctly detected 76 of 88 (86%) stenoses, and recognized 242 of 302 (80%) not affected segments. The Pearson correlation coefficient between MRCA and CA in assessing coronary narrowings was very high: r = 0.85. Despite this the mean difference was 4.5 with a standard error of estimate of 0.21, indicating that MRCA slightly overestimates the degree of stenoses. CONCLUSIONS: Our study showed that 2D breath-hold MRCA is an accurate technique in displaying and quantifying the most significant stenoses in the proximal and middle segments of the coronary arteries.

The common mutations in the lipoprotein lipase gene in Italy: effects on plasma lipids and angiographically assessed coronary atherosclerosis.

The present study evaluated the role of the common lipoprotein lipase (LPL) mutations on the risk of dyslipidemia and coronary atherosclerosis in an Italian population. Cohorts of 632 patients undergoing coronary angiography, as well as 191 healthy controls, were screened by a combination of PCR and restriction enzyme digestion. In the pooled population, the frequencies of LPL D9N and N291S were 4.1%, with no homozygous carriers, whereas that of LPL S447X was 21% with 19.6% heterozygous and 1.4% homozygous carriers. Compared to non-carriers, LPL N291S carriers showed higher plasma triglycerides (TG) (p < 0.03) and increased risk of high TG phenotype (odds ratio [OR] 2.49, 95% Cl 1.06-5.81; p < 0.03). When this LPL mutation was associated with high body mass index (BMI) ( > 25 Kg/m2) or fasting, plasma insulin (> 10.6 mU ml(-1)) significantly reduced HDL-C levels were also observed. Carriers of the S447X mutation presented with higher HDL-C concentrations (p < 0.05) as compared to non-carriers; they also showed a significantly reduced risk of high TG/low HDL-C dyslipidemia (OR 0.34, 95%, Cl 0.12-0.99; p < 0.05). The favourable effect of the LPL S447X variant was even more pronounced in lean subjects and in those with low insulin levels. No significant influence on plasma lipids by the LPL D9N was observed. None of LPL variants was a significant predictor of angiographically assessed coronary atherosclerosis. At most, the risk was borderline, increased in N291S carriers and possibly decreased in S447X carriers.

A common mutation of the insulin receptor substrate-1 gene is a risk factor for coronary artery disease.

Insulin resistance is associated with increased risk of atherosclerosis. Insulin receptor substrate-1 (IRS-1) plays a key role in tissue insulin sensitivity. A common mutation (G972R) of the IRS-1 gene has been shown to impair IRS-1 function, and it has been associated with reduced insulin sensitivity and lipid abnormalities. This led us to investigate the role of the G972R mutation in predisposing individuals to coronary artery disease (CAD). The DNA of 318 subjects with angiographically documented coronary atherosclerosis (>50% stenosis) and 208 population control subjects was analyzed for the presence of the G972R mutation. This mutation was detected by nested polymerase chain reaction and BstNI restriction enzyme digestion. The frequency of the G972R mutation was significantly higher among patients with CAD than controls (18. 9% versus 6.8%, respectively; P<0.001). After controlling for other coronary risk factors, the relative risk of CAD associated with the G972R mutation was 2.93 (95% CI 1.30 to 6.60; P<0.02) in the entire cohort. This risk was found to be even higher in the subgroups of obese subjects (odds ratio [OR] 6.97, 95% CI 2.24 to 21.4; P<0.001) and subjects with clinical features of insulin resistance syndrome (OR 27.3, 95% CI 7.19 to 104.0; P<0.001). The IRS-1 gene variant was associated with a higher frequency of diabetes mellitus (14.9% among carriers versus 6.5% among noncarriers; P<0.01) and with a 60% increase of plasma total triglycerides (P<0.001). Also, plasma concentrations of total cholesterol and the ratio of total cholesterol to HDL cholesterol were significantly (P<0.001) higher among carriers than noncarriers, although to lesser a extent. These effects were independent of CAD status. The G972R mutation in the IRS-1 gene was found to be a significant independent predictor of CAD. Moreover, this mutation greatly increased the risk of CAD in obese subjects and in patients with the cluster of abnormalities of insulin resistance syndrome. Besides the increased frequency of diabetes, carriers showed a more atherogenic lipid profile, suggesting a potential role of the IRS-1 gene in the pathogenesis of lipid abnormalities associated with CAD.

Enoximone coupled to very low dose dobutamine echocardiography detects myocardial viability in akinetic and dyskinetic post-myocardial infarcted areas.

Dobutamine and enoximone stimulate independently inotropic reserve by increasing intracellular cyclic adenosine monophosphate. The potential of enoximone (0.75 mg/kg body weight over 10 minutes) followed by very low dose (2.5 microg/kg/min) dobutamine echocardiography to predict recovery of ventricular function in akinetic and dyskinetic postinfarcted areas was studied. We enrolled 22 patients with previous Q-wave myocardial infarction and regional wall motion abnormalities related to left anterior descending arterial disease, left ventricular ejection fraction <40%, and all scheduled for myocardial revascularization. A 10 microg/kg/min dobutamine test was performed 48 hours before the study protocol. Test images obtained at peak of pharmacodynamic effects were compared with those obtained at 4 months after myocardial revascularization. We used a 16-segment ventricular model and a 5-grade scoring system. Resting regional myocardial dysfunction graded > or =2 was present in 267 of 352 segments evaluated. Contractile reserve (decrease in resting wall motion score > or =2 grades) at peak effect of enoximone infusion was present in 34 of 112 severely hypokinetic, 42 of 117 akinetic, and 14 of 38 dyskinetic segments. The inotropic reserve evaluated after very low dose dobutamine was observed in 34 of 112 severely hypokinetic, 49 of 117 akinetic, and 20 of 38 dyskinetic segments. After revascularization, recovery of function was observed in 31 of 112 severely hypokinetic, 49 of 117 akinetic, and 21 of 38 dyskinetic segments. Overall, there was a significant correlation between absolute score changes of segments which were abnormal at baseline (n = 267) to enoximone peak effects (r = 0.49, p <0.001) to predict absolute changes after revascularization; after dobutamine there was progress toward identity (r = 0.62, p <0.001) and the difference was significant among correlation slopes of dobutamine alone, enoximone alone, and enoximone plus very low dose dobutamine echocardiograophy (0.45+/-0.04, 0.51+/-0.04, and 0.63+/-0.04, respectively, F = 5.25, p = 0.005). Therefore, enoximone followed by very low dose dobutamine may assess myocardial viability of postinfarcted akinetic and dyskinetic areas. This test may be useful when evaluating patients with more severe cardiac failure and/or life-threatening arrhythmias.

Recovery of contractility of viable myocardium during inotropic stimulation is not dependent on an increase of myocardial blood flow in the absence of collateral filling.

OBJECTIVES: The purpose of this study was to determine whether contractile recovery induced by dobutamine in dysfunctioning viable myocardium supplied by nearly occluded vessels is related to an increase in blood flow in the absence of collaterals. BACKGROUND: Dobutamine is used to improve contractility in ventricular dysfunction during acute myocardial infarction. However, it is unclear whether a significant increase in regional blood flow may be involved in dobutamine effect. METHODS: Twenty patients with 5- to 10-day old anterior infarction and > or =90% left anterior descending coronary artery stenosis underwent 99mTc-Sestamibi tomography (to assess myocardial perfusion) at rest and during low dose (5 to 10 microg/kg/min) dobutamine echocardiography. Rest echocardiography and scintigraphy were repeated >1 month after revascularization. Nine patients had collaterals to the infarcted territory (group A), and 11 did not (group B). RESULTS: Baseline wall motion score was similar in both groups (score 15.9+/-1.3 vs. 17.4+/-2.0, p = NS), whereas significant changes at dobutamine and postrevascularization studies were detected (F[2,30] = 409.79, p < 0.0001). Wall motion score improved significantly (p < 0.001) in group A both at dobutamine (-5.3+/-2.2) and at postrevascularization study (-5.5+/-1.9), as well as in group B (-3.9+/-2.8 and -4.5+/-2.4, respectively). Baseline 99mTc-Sestamibi uptake was similar in both groups (62.9+/-9.7% vs. 60.3+/-10.4%, p = NS), whereas at dobutamine and postrevascularization studies a significant change (F[2,30] = 65.17, p < 0.0001) and interaction between the two groups (F[2,30] = 33.14, p < 0.0001) were present. Tracer uptake increased significantly in group A both at dobutamine (+ 10.9+/-7.9%, p < 0.001) and at postrevascularization study (12.1+/-8.7%, p < 0.001). Conversely, group B patients showed no change in tracer uptake after dobutamine test (-0.4+/-5.8, p = NS), but only after revascularization (+8.8+/-7.2%, p < 0.001). CONCLUSIONS: The increase in contractility induced by low dose dobutamine infusion in dysfunctional viable myocardium supplied by nearly occluded vessels occurs even in the absence of a significant increase in blood flow.