Endothelial function and insulin sensitivity during acute non-esterified fatty acid elevation: effects of fat composition and gender

Background and Aims: We have reported that adverse effects on flow-mediated dilation of an acute elevation of non-esterified fatty acids rich in saturated fat (SFA) are reversed following addition of long-chain (LC) n-3 polyunsaturated fatty acids (PUFA), and hypothesised that these effects may be mediated through alterations in insulin signalling pathways. In a subgroup, we explored the effects of raised NEFA enriched with SFA, with or without LC n-3 PUFA, on whole body insulin sensitivity (SI) and responsiveness of the endothelium to insulin infusion. Methods and Results: Thirty adults (mean age 27.8 y, BMI 23.2 kg/m2) consumed oral fat loads on separate occasions with continuous heparin infusion to elevate NEFA between 60-390 min. For the final 150 min, a hyperinsulinaemic-euglycaemic clamp was performed, whilst FMD and circulating markers of endothelial function were measured at baseline, pre-clamp (240 min) and post-clamp (390 min). NEFA elevation during the SFA-rich drinks was associated with impaired FMD (P=0.027) whilst SFA+LC n-3 PUFA improved FMD at 240 min (P=0.003). In males, insulin infusion attenuated the increase in FMD with SFA+LC n-3 PUFA (P=0.049), with SI 10% greater with SFA+LC n-3 PUFA than SFA (P=0.041). Conclusion: This study provides evidence that NEFA composition during acute elevation influences both FMD and SI, with some indication of a difference by gender. However our findings are not consistent with the hypothesis that the effects of fatty acids on endothelial function and SI operate through a common pathway. Trial registered at clinicaltrials.gov, NCT01351324.

Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction and cause-specific mortality : cohort study

Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective. Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991–1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163). Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03–1.19; and 1.11, 1.02–1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09–1.37; and 1.18, 1.04–1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample. Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.

Prevalence and predictors of ventricular remodeling after anterior myocardial infarction in the era of modern medical therapy

Background: The consequences of aggressive therapy following a myocardial infarction (MI) on ventricular remodeling are not well established. Thus, the objective of this study was to analyze the prevalence, clinical characteristics, and predictors of left ventricular remodeling in the era of modern medical therapy.Material/Methods: Clinical characteristics and echocardiographic data were analyzed in 66 consecutive patients with anterior infarction at admission and at 6-month follow-up. Ventricular remodeling was defined as an increase of 10% in ventricular end-systolic or end-diastolic diameter.Results: In our study, 58% of patients presented with ventricular remodeling. Patients with remodeling possessed higher total plasma creatine kinase (CPK), MB-fraction (CPK-MB), heart rate, heart failure, shortness of breath, and reperfusion therapy than patients without remodeling. In contrast, patients with remodeling had a smaller ejection fraction, E-Wave deceleration time (EDT), and early (E' Wave) and late (A' Wave) diastolic mitral annulus velocity (average of septal and lateral walls), but a higher E/E' than patients without remodeling. Patients with remodeling used more diuretics, digoxin, oral anticoagulants and aldosterone antagonists than patients without remodeling. In the multivariate analyses, only E' Wave was an independent predictor of ventricular remodeling. Each 1 unit increase in the E' Wave was associated with a 59% increased odds of ventricular remodeling.Conclusions: In patients with anterior MI, despite contemporary treatment, ventricular remodeling is still a common event. In addition, diastolic function can have an important role as a predictor of remodeling in this scenario.

Fondaparinux em intervenção coronária percutânea no tratamento da síndrome coronária aguda

Background: Fondaparinux is considered an agent with a well-established safety and efficacy profile in the treatment of non-ST segment elevation acute coronary syndromes, but when used alone, is associated to a higher incidence of thrombotic complications during invasive coronary procedures, requiring the supplementation of an anti-IIa agent. This study aimed to evaluate the efficacy and safety of percutaneous coronary intervention (PCI) in patients with non-ST segment elevation acute coronary syndromes previously treated with fondaparinux. Methods: Prospective, controlled registry enrolling 127 consecutive patients submitted to an early invasive stratification during treatment with fondaparinux, with supplementation of intravenous unfractionated heparin at a dose of 85 U/kg at the time of PCI. Results: The rate of the composite primary endpoint including death, acute myocardial infarction, stroke, stent thrombosis or emergency myocardial revascularization was 3.2%. The cumulative incidence of major bleeding and vascular complications was 3.2%. There were no cases of guidecatheter thrombosis or abrupt vessel closure. Conclusions: PCI in patients with acute coronary syndromes receiving fondaparinux is associated with a low rate of major adverse cardiovascular ischemic events and severe hemorrhagic complications. Supplementation of unfractionated heparin during the invasive procedures eliminates the risk of catheter-related thrombosis.

Waist circumference, but not body mass index, is a predictor of ventricular remodeling after anterior myocardial infarction

Objective: The impact of obesity on ventricular remodeling after myocardial infarction (MI) is still poorly understood. Therefore, the aim of this study was to evaluate the role of waist circumference (WC) and body mass index as predictors of cardiac remodeling in patients after an anterior MI. Methods: Eighty-three consecutive patients with anterior MI were prospectively evaluated. Clinical characteristics and echocardiographic data were analyzed at admission and at a 6-mo follow-up. Ventricular remodeling was defined as a 10% increase in left ventricular end-systolic or end-diastolic diameter at the 6-mo follow-up. Results: In our study, 83 consecutive patients were evaluated (72% men). Ventricular remodeling was present in 31% of the patients (77% men). Patients with remodeling had higher creatine phosphokinase and creatine phosphokinase-MB peak values, a higher resting heart rate, a larger left atrial diameter, and a larger interventricular septum diastolic thickness. In addition, patients with remodeling had lower peak velocity of early ventricular filling deceleration time and ejection fraction. Patients with remodeling presented higher WC values (with remodeling, 99.2 ± 10.4 cm; without remodeling, 93.9 ± 10.8 cm, P = 0.04), but there were no differences in the body mass index values. In the logistic regression analysis, WC, adjusted by age, gender, ejection fraction, and creatine phosphokinase levels, was an independent predictor of left ventricular remodeling (odds ratio 1.067, 95% confidence interval 1.001-1.129, P = 0.02). Conclusion: Waist circumference, but not body mass index, is a predictor of ventricular remodeling after an anterior MI. Therefore, the WC of these patients should be measured in clinical practice. © 2013 Elsevier Inc.

Assessment of myocardial infarction by CT angiography and cardiovascular MRI in patients with cocaine-associated chest pain: a pilot study

Objectives: Cocaine is a commonly used illicit drug that leads to the most emergency department (ED) visits. Chest pain is the most common presentation, reported in 40% of patients. Our aim was to evaluate the incidence of previous myocardial infarction among young cocaine users (18-40 years) with cocaine-associated chest pain by the assessment of myocardial fibrosis by cardiovascular MRI. Second, we also intended to evaluate the coronary tree by CT angiography (CTA). Methods: 24 cocaine users (22 males) who frequently complained about cocaine-associated chest pain underwent CTA and cardiovascular MRI. Mean age of patients was 29.7 years and most of them (79%) had frequently used inhalatory cocaine. Results: The calcium score turned out to be positive in only one patient (Agatston=54). Among the coronary segments evaluated, only one patient had calcified plaques at the anterior descending coronary artery (proximal and medium segments). Assessment of regional ventricular function by the evaluation of 17 segments was normal in all patients. None of the patients showed myocardial delayed enhancement, indicative of myocardial fibrosis. CTA therefore confirmed the low cardiovascular risk of these patients, since most of them (96%) had no atherosclerosis detected by this examination. Only one patient (4%) had coronary atherosclerosis detected, without significant coronary stenosis. Conclusion: Cardiovascular MR did not detect the presence of delayed enhancement indicative of myocardial fibrosis among young cocaine users with low cardiovascular risk who had complained of cocaine-associated chest pain.

Chronic Stress Improves the Myocardial Function without Altering L-type Ca+2 Channel Activity in Rats

Background: Chronic stress is associated with cardiac remodeling; however the mechanisms have yet to be clarified. Objective: The purpose of this study was test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca2+ channel activity depression. Methods: Thirty-day-old male Wistar rats (70 - 100 g) were distributed into two groups: control (C) and chronic stress (St). The stress was consistently maintained at immobilization during 15 weeks, 5 times per week, 1h per day. The cardiac function was evaluated by left ventricular performance through echocardiography and by ventricular isolated papillary muscle. The myocardial papillary muscle activity was assessed at baseline conditions and with inotropic maneuvers such as: post-rest contraction and increases in extracellular Ca2+ concentration, in presence or absence of specific blockers L-type calcium channels. Results: The stress was characterized for adrenal glands hypertrophy, increase of systemic corticosterone level and arterial hypertension. The chronic stress provided left ventricular hypertrophy. The left ventricular and baseline myocardial function did not change with chronic stress. However, it improved the response of the papillary muscle in relation to positive inotropic stimulation. This function improvement was not associated with the L-type Ca2+ channel. Conclusion: Chronic stress produced cardiac hypertrophy; however, in the study of papillary muscle, the positive inotropic maneuvers potentiated cardiac function in stressed rats, without involvement of L-type Ca2+ channel. Thus, the responsible mechanisms remain unclear with respect to Ca2+ influx alterations. (Arq Bras Cardiol 2012;99(4):907-914)

Coronary plaque rupture in patients with myocardial infarction after noncardiac surgery: Frequent and dangerous

Purpose: The pathophysiology of acute coronary syndromes (ACS) after noncardiac surgery is not established yet. Thrombosis over a vulnerable plaque or decreased oxygen supply secondary to anemia or hypotension may be involved. The purpose of this study was to investigate the pathophysiology of ACS complicating noncardiac surgery. Methods: Clinical and angiographic data were prospectively recorded into a database for 120 consecutive patients that had an ACS after noncardiac surgery (PACS), for 120 patients with spontaneous ACS (SACS), and 240 patients with stable coronary artery disease (CAD). Coronary lesions with obstructions greater than 50% were classified based on two criteria: Ambrose's classification and complex morphology. The presence of Ambrose's type II or complex lesions were compared between the three groups. Results: We analyzed 1470 lesions in 480 patients. In PACS group, 45% of patients had Ambrose's type II lesions vs. 56.7% in SACS group and 16.4% in stable CAD group (P < 0.001). Both PACS and SACS patients had more complex lesions than patients in stable CAD group (56.7% vs. 79.2% vs. 31.8%, respectively; P < 0.001). Overall, the independent predictors of plaque rupture were being in the group PACS (P < 0.001, OR 2.86; CI, 1.82-4.52 for complex lesions and P < 0.001, OR 3.43; CI, 2.1-5.6 for Ambrose's type II lesions) or SACS (P < 0.001, OR 8.71; CI, 5.15-14.73 for complex lesions and P < 0.001, OR 5.99; CI, 3.66-9.81 for Ambrose's type II lesions). Conclusions: Nearly 50% of patients with perioperative ACS have evidence of coronary plaque rupture, characterizing a type 1 myocardial infarction. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Momentary stress moderates procoagulant reactivity to a trauma-specific interview in patients with posttraumatic stress disorder caused by myocardial infarction

Hypercoagulability of the blood might partially explain the increased cardiovascular disease risk in posttraumatic stress disorder (PTSD) and is also triggered by anticipatory stress. We hypothesized exaggerated procoagulant reactivity in patients with PTSD in response to a trauma-specific interview that would be moderated by momentary stress levels. We examined 23 patients with interviewer-diagnosed PTSD caused by myocardial infarction (MI) and 21 post-MI patients without PTSD. A second diagnostic (i.e., trauma-specific) interview to assess posttraumatic stress severity was performed after a median follow-up of 26 months (range 12-36). Before that interview patients rated levels of momentary stress (Likert scale 0-10) and had blood collected before and after the interview. The interaction between PTSD diagnostic status at study entry and level of momentary stress before the follow-up interview predicted reactivity of fibrinogen (P=0.036) and d-dimer (P=0.002) to the PTSD interview. Among patients with high momentary stress levels, PTSD patients had greater fibrinogen (P=0.023) and d-dimer (P=0.035) reactivity than non-PTSD patients. Among patients with low momentary stress levels, PTSD patients had less d-dimer reactivity than non-PTSD patients (P=0.024); fibrinogen reactivity did not significantly differ between groups. Momentary stress levels, but not severity of posttraumatic stress, correlated with d-dimer reactivity in PTSD patients (r=0.46, P=0.029). We conclude that momentary stress levels moderated the relationship between PTSD and procoagulant reactivity to a trauma-specific interview. Procoagulant reactivity in post-MI patients with PTSD confronted with their traumatically experienced MI was observed if patients perceived high levels of momentary stress before the interview.

Postmortem unenhanced magnetic resonance imaging of myocardial infarction in correlation to histological infarction age characterization

AIMS: Postmortem magnetic resonance (MRI) imaging is currently evaluated as alternative to traditional autopsy and myocardial infarction plays a key role therein. The aim of this study is to determine the suitability of postmortem MRI in infarction age staging. METHODS AND RESULTS: In eight human forensic corpses presenting with a total of 11 myocardial infarcted areas, short-axis, transversal, and longitudinal long-axis images (T1, T2, stir, flair) were acquired in situ on a 1.5 T system. During subsequent autopsy, the section technique was adapted to short-axis images. Histological investigations were performed along the entire circumference of the left ventricle to correlate the signal alteration in MR to the histological appearance. Two peracute infarctions were not detected in MRI and autopsy. Four acute infarcted areas presented with decreased signal in necrotic centres and increased signal in marginal myocardial regions (T2-weighted). T1-weighted images showed local hyperintensities when intramyocardial haemorrhage occurred. Four cases showed subacute infarctions with hyperintense regions in T2-weighted images and no signal alteration in T1-weighted images. Four chronic myocardial infarctions showed distinctively decreased signals in all applied sequences. CONCLUSION: Postmortem MRI demonstrates myocardial infarction in situ and allows for an infarction age estimation based on the signal behaviour.

Noninvasive Doppler-derived myocardial performance index in rats with myocardial infarction: validation and correlation by conductance catheter

The rodent model of myocardial infarction (MI) is extensively used in heart failure studies. However, long-term follow-up of echocardiographic left ventricular (LV) function parameters such as the myocardial performance index (MPI) and its ratio with the fractional shortening (LVFS/MPI) has not been validated in conjunction with invasive indexes, such as those derived from the conductance catheter (CC). Sprague-Dawley rats with left anterior descending coronary artery ligation (MI group, n = 9) were compared with a sham-operated control group (n = 10) without MI. Transthoracic echocardiography (TTE) was performed every 2 wk over an 8-wk period, after which classic TTE parameters, especially MPI and LVFS/MPI, were compared with invasive indexes obtained by using a CC. Serial TTE data showed significant alterations in the majority of the noninvasive functional and structural parameters (classic and novel) studied in the presence of MI. Both MPI and LVFS/MPI significantly (P < 0.05 for all reported values) correlated with body weight (r = -0.58 and 0.76 for MPI and LVFS/MPI, respectively), preload recruitable stroke work (r = -0.61 and 0.63), LV end-diastolic pressure (LVEDP) (r = 0.82 and -0.80), end-diastolic volume (r = 0.61 and -0.58), and end-systolic volume (r = 0.46 and -0.48). Forward stepwise linear regression analysis revealed that, of all variables tested, LVEDP was the only independent determinant of MPI (r = 0.84) and LVFS/MPI (r = 0.83). We conclude that MPI and LVFS/MPI correlate strongly and better than the classic noninvasive TTE parameters with established, invasively assessed indexes of contractility, preload, and volumetry. These findings support the use of these two new noninvasive indexes for long-term analysis of the post-MI LV remodeling.

The effect of a myocardial infarction on the normalized time-varying elastance curve

It has been suggested that the shape of the normalized time-varying elastance curve [E(n)(t(n))] is conserved in different cardiac pathologies. We hypothesize, however, that the E(n)(t(n)) differs quantitatively after myocardial infarction (MI). Sprague-Dawley rats (n = 9) were anesthetized, and the left anterior descending coronary artery was ligated to provoke the MI. A sham-operated control group (CTRL) (n = 10) was treated without the MI. Two months later, a conductance catheter was inserted into the left ventricle (LV). The LV pressure and volume were measured and the E(n)(t(n)) derived. Slopes of E(n)(t(n)) during the preejection period (alpha(PEP)), ejection period (alpha(EP)), and their ratio (beta = alpha(EP)/alpha(PEP)) were calculated, together with the characteristic decay time during isovolumic relaxation (tau) and the normalized elastance at end diastole (E(min)(n)). MI provoked significant LV chamber dilatation, thus a loss in cardiac output (-33%), ejection fraction (-40%), and stroke volume (-30%) (P < 0.05). Also, it caused significant calcium increase (17-fold), fibrosis (2-fold), and LV hypertrophy. End-systolic elastance dropped from 0.66 +/- 0.31 mmHg/microl (CTRL) to 0.34 +/- 0.11 mmHg/microl (MI) (P < 0.05). Normalized elastance was significantly reduced in the MI group during the preejection, ejection, and diastolic periods (P < 0.05). The slope of E(n)(t(n)) during the alpha(PEP) and beta were significantly altered after MI (P < 0.05). Furthermore, tau and end-diastolic E(min)(n) were both significantly augmented in the MI group. We conclude that the E(n)(t(n)) differs quantitatively in all phases of the heart cycle, between normal and hearts post-MI. This should be considered when utilizing the single-beat concept.

Myocardial infarction due to paradoxical embolism in a patient with large atrial septal defect

We present the case of a patient who presented with acute inferior myocardial infarction and embolic occlusion of the distal left anterior descending and proximal right coronary artery. A large atrial septal defect (ASD) was seen on transesophageal echocardiography and the ASD was closed during the same session as coronary angiography and percutaneous coronary intervention. The presence of embolic or thrombotic occlusions of coronary arteries should prompt interventional cardiologists to look for a patent foramen ovale or ASD and perform percutaneous closure right away.

Surgical versus percutaneous revascularization of coronary artery disease in diabetic patients

Morbidity and mortality related to coronary artery disease (CAD) remain a great challenge in patients with diabetes mellitus. Revascularization of CAD is an important therapeutic intervention owing to its impact on both symptoms and prognosis. The optimal revascularization strategy continues to evolve due to the advent of new technologies and improved peri-procedural outcome with both percutaneous coronary interventions and coronary artery bypass grafting. Although clinical outcome following coronary artery bypass is worse in diabetic as opposed to non-diabetic patients, surgical revascularization tends to be associated with better outcome in stable patients with multivessel disease and reduced left ventricular function. The advent of drug-eluting stents has challenged the supremacy of coronary artery bypass grafting and has become a valuable alternative to surgery. The safety and efficacy of drug-eluting stents in the treatment of patients with diabetes and multivessel disease is currently under investigation in several ongoing randomized controlled trials. Percutaneous coronary intervention is the therapy of choice in patients with acute coronary syndromes, particularly ST-elevation myocardial infarction. The focus of this review is to present the current evidence, define the role of percutaneous and surgical revascularization in the treatment of diabetic patients with CAD, and propose a tailored approach for clinical decision-making.

Coronary artery injury due to catheter ablation in adults: presentations and outcomes

BACKGROUND: Currently, only anecdotal information exists on the presentation and outcome of coronary arterial injury after ablation procedures. METHODS AND RESULTS: Four patients who sustained coronary artery injury of a cohort of patients undergoing 4655 consecutive ablation procedures (0.09%) are described. The patients' mean age was 45+/-11 years, and 1.8+/-0.5 prior ablation attempts had been unsuccessful. Coronary injury occurred from epicardial ventricular tachycardia ablation in 2 patients (irrigated radiofrequency ablation in one and cryoablation in the other) and ablation within the middle cardiac vein with irrigated radiofrequency in 2 patients. All involved branches of the right coronary artery. Acute occlusion presenting with ST-segment elevation immediately after ablation was recognized during the procedure in 2 cases. Occlusion failed to respond to nitroglycerin or balloon dilation, and stenting was required in both cases. Acute myocardial infarction occurred 2 weeks after epicardial ablation as a result of occlusion of a right ventricular branch of the right coronary artery giving rise to the posterior descending coronary artery in 1 patient. A moderate asymptomatic stenosis was seen on angiography after epicardial cryoablation in 1 patient. All patients recovered and remained asymptomatic from the coronary injury and arrhythmias during 37+/-53 months of follow-up. CONCLUSIONS: Coronary arterial injury after ablation procedures is rare. It may present acutely or several weeks after an ablation procedure. Acute occlusion appears to require coronary stenting. Unanticipated anatomic variations can predispose to coronary injury.