Thrombus formation in the left ventricle after large myocardial infarction – assessment with cardiac magnetic resonance imaging

INTRODUCTION Left ventricular thrombus (LVT) formation may worsen the post-infarct outcome as a result of thromboembolic events. It also complicates the use of modern antiplatelet regimens, which are not compatible with long-term oral anticoagulation. The knowledge of the incidence of LVT may therefore be of importance to guide antiplatelet and antithrombotic therapy after acute myocardial infarction (AMI). METHODS In 177 patients with large, mainly anterior AMI, standard cardiac magnetic resonance imaging (CMR) including cine and late gadolinium enhancement (LGE) imaging was performed shortly after AMI as per protocol. CMR images were analysed at an independent core laboratory blinded to the clinical data. Transthoracic echocardiography (TTE) was not mandatory for the trial, but was performed in 64% of the cases following standard of care. In a logistic model, 3 out of 61 parameters were used in a multivariable model to predict LVT. RESULTS LVT was detected by use of CMR in 6.2% (95% confidence interval [CI] 3.1%-10.8%). LGE sequences were best to detect LVT, which may be missed in cine sequences. We identified body mass index (odds ratio 1.18; p = 0.01), baseline platelet count (odds ratio 1.01, p = 0.01) and infarct size as assessed by use of CMR (odds ratio 1.03, p = 0.02) as best predictors for LVT. The agreement between TTE and CMR for the detection of LVT is substantial (kappa = 0.70). DISCUSSION In the current analysis, the incidence of LVT shortly after AMI is relatively low, even in a patient population at high risk. An optimal modality for LVT detection is LGE-CMR but TTE has an acceptable accuracy when LGE-CMR is not available.

Perspectives on the 2014 ESC/EACTS Guidelines on Myocardial Revascularization: Fifty Years of Revascularization: Where Are We and Where Are We Heading?

The joint European Society of Cardiology and European Association of Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization collect and summarize the evidence regarding decision-making, diagnostics, and therapeutics in various clinical scenarios of coronary artery disease, including elective, urgent, and emergency settings. The 2014 document updates and extends the effort started in 2010, year of the first edition of these guidelines. Importantly, this latest edition provides a systematic review of all randomized clinical trials performed since 1980, comparing different strategies of myocardial revascularization, including coronary artery bypass graft (CABG), balloon angioplasty, percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and first- and second-generation drug-eluting stents (DES). This review aims to highlight the most relevant novelties introduced by the 2014 edition of the ESC/EACTS myocardial revascularization guidelines as compared with the previous edition and to describe similarities and differences with the American societies' guidelines.

Benefits and Risks of Extended Duration Dual Antiplatelet Therapy After PCI in Patients With and Without Acute Myocardial Infarction

BACKGROUND The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations. OBJECTIVES This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI. METHODS The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding. RESULTS Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p < 0.001; no MI group, 0.4% vs. 1.1%, p < 0.001; interaction p = 0.69). The reduction in MACCE for continued thienopyridine was greater for patients with MI (3.9% vs. 6.8%; p < 0.001) compared with those with no MI (4.4% vs. 5.3%; p = 0.08; interaction p = 0.03). In both groups, continued thienopyridine reduced MI (2.2% vs. 5.2%, p < 0.001 for MI; 2.1% vs. 3.5%, p < 0.001 for no MI; interaction p = 0.15) but increased bleeding (1.9% vs. 0.8%, p = 0.005 for MI; 2.6% vs. 1.7%, p = 0.007 for no MI; interaction p = 0.21). CONCLUSIONS Compared with 12 months of therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study [The DAPT Study]; NCT00977938).

Comparison of prasugrel and clopidogrel-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention: A propensity score-matched analysis of the Acute Myocardial Infarction in Switzerland (AMIS)-Plus Registry

OBJECTIVE The purpose of this study was to investigate outcomes of patients treated with prasugrel or clopidogrel after percutaneous coronary intervention (PCI) in a nationwide acute coronary syndrome (ACS) registry. BACKGROUND Prasugrel was found to be superior to clopidogrel in a randomized trial of ACS patients undergoing PCI. However, little is known about its efficacy in everyday practice. METHODS All ACS patients enrolled in the Acute Myocardial Infarction in Switzerland (AMIS)-Plus registry undergoing PCI and being treated with a thienopyridine P2Y12 inhibitor between January 2010-December 2013 were included in this analysis. Patients were stratified according to treatment with prasugrel or clopidogrel and outcomes were compared using propensity score matching. The primary endpoint was a composite of death, recurrent infarction and stroke at hospital discharge. RESULTS Out of 7621 patients, 2891 received prasugrel (38%) and 4730 received clopidogrel (62%). Independent predictors of in-hospital mortality were age, Killip class >2, STEMI, Charlson comorbidity index >1, and resuscitation prior to admission. After propensity score matching (2301 patients per group), the primary endpoint was significantly lower in prasugrel-treated patients (3.0% vs 4.3%; p=0.022) while bleeding events were more frequent (4.1% vs 3.0%; p=0.048). In-hospital mortality was significantly reduced (1.8% vs 3.1%; p=0.004), but no significant differences were observed in rates of recurrent infarction (0.8% vs 0.7%; p=1.00) or stroke (0.5% vs 0.6%; p=0.85). In a predefined subset of matched patients with one-year follow-up (n=1226), mortality between discharge and one year was not significantly reduced in prasugrel-treated patients (1.3% vs 1.9%, p=0.38). CONCLUSIONS In everyday practice in Switzerland, prasugrel is predominantly used in younger patients with STEMI undergoing primary PCI. A propensity score-matched analysis suggests a mortality benefit from prasugrel compared with clopidogrel in these patients.

Myocardial expression profiles of candidate molecules in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia compared to those with dilated cardiomyopathy and healthy controls.

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is mainly an autosomal dominant disease characterized by fibrofatty infiltration of the right ventricle, leading to ventricular arrhythmias. Mutations in desmosomal proteins can be identified in about half of the patients. The pathogenic mechanisms leading to disease expression remain unclear. OBJECTIVE The purpose of this study was to investigate myocardial expression profiles of candidate molecules involved in the pathogenesis of ARVC/D. METHODS Myocardial messenger RNA (mRNA) expression of 62 junctional molecules, 5 cardiac ion channel molecules, 8 structural molecules, 4 apoptotic molecules, and 6 adipogenic molecules was studied. The averaged expression of candidate mRNAs was compared between ARVC/D samples (n = 10), nonfamilial dilated cardiomyopathy (DCM) samples (n = 10), and healthy control samples (n = 8). Immunohistochemistry and quantitative protein expression analysis were performed. Genetic analysis using next generation sequencing was performed in all patients with ARVC/D. RESULTS Following mRNA levels were significantly increased in patients with ARVC/D compared to those with DCM and healthy controls: phospholamban (P ≤ .001 vs DCM; P ≤ .001 vs controls), healthy tumor protein 53 apoptosis effector (P = .001 vs DCM; P ≤ .001 vs controls), and carnitine palmitoyltransferase 1β (P ≤ .001 vs DCM; P = 0.008 vs controls). Plakophillin-2 (PKP-2) mRNA was downregulated in patients with ARVC/D with PKP-2 mutations compared with patients with ARVC/D without PKP-2 mutations (P = .04). Immunohistochemistry revealed significantly increased protein expression of phospholamban, tumor protein 53 apoptosis effector, and carnitine palmitoyltransferase 1β in patients with ARVC/D and decreased PKP-2 expression in patients with ARVC/D carrying a PKP-2 mutation. CONCLUSION Changes in the expression profiles of sarcolemmal calcium channel regulation, apoptosis, and adipogenesis suggest that these molecular pathways may play a critical role in the pathogenesis of ARVC/D, independent of the underlying genetic mutations.

Resilience as a correlate of acute stress disorder symptoms in patients with acute myocardial infarction

OBJECTIVES Myocardial infarction (MI) may be experienced as a traumatic event causing acute stress disorder (ASD). This mental disorder has an impact on the daily life of patients and is associated with the development of post-traumatic stress disorder. Trait resilience has been shown to be a protective factor for post-traumatic stress disorder, but its association with ASD in patients with MI is elusive and was examined in this study. METHODS We investigated 71 consecutive patients with acute MI within 48 h of having stable haemodynamic conditions established and for 3 months thereafter. All patients completed the Acute Stress Disorder Scale and the Resilience Scale to self-rate the severity of ASD symptoms and trait resilience, respectively. RESULTS Hierarchical regression analysis showed that greater resilience was associated with lower symptoms of ASD independent of covariates (b=-0.22, p<0.05). Post hoc analysis revealed resilience level to be inversely associated with the ASD symptom clusters of re-experiencing (b=-0.05, p<0.05) and arousal (b=-0.09, p<0.05), but not with dissociation and avoidance. CONCLUSIONS The findings suggest that patients with acute MI with higher trait resilience experience relatively fewer symptoms of ASD during MI. Resilience was particularly associated with re-experiencing and arousal symptoms. Our findings contribute to a better understanding of resilience as a potentially important correlate of ASD in the context of traumatic situations such as acute MI. These results emphasise the importance of identifying patients with low resilience in medical settings and to offer them adequate support.

Association of Trait Resilience With Peritraumatic and Posttraumatic Stress in Patients With Myocardial Infarction.

OBJECTIVE Acute myocardial infarction (MI) is a life-threatening condition, leading to immediate fear and distress in many patients. Approximately 18% of patients develop posttraumatic stress disorder in the aftermath of MI. Trait resilience has shown to be a protective factor for the development of posttraumatic stress disorder. However, whether this buffering effect has already an impact on peritraumatic distress and applies to patients with MI is elusive. METHODS We investigated 98 consecutive patients with acute MI within 48 hours after having reached stable circulatory conditions and 3 months thereafter. Peritraumatic distress was assessed retrospectively with three single-item questions about pain, fear, and helplessness during MI. All patients completed the Posttraumatic Diagnostic Scale (PDS) and the Resilience Scale to self-rate posttraumatic stress and trait resilience. RESULTS Multivariate models adjusting for sociodemographic and medical factors showed that trait resilience was not associated with peritraumatic distress, but significantly so with posttraumatic stress. Patients with greater trait resilience showed lower PDS scores (b = -0.06, p < .001). There was no significant relationship between peritraumatic distress scores and PDS scores; resilience did not emerge as a moderator of this relationship. CONCLUSIONS The findings suggest that trait resilience does not buffer the perception of acute MI as stressful per se but may enhance better coping with the traumatic experience in the longer term, thus preventing the development of MI-associated posttraumatic stress. Trait resilience may play an important role in posttraumatic stress symptoms triggered by medical diseases such as acute MI.

Perception of a hectic hospital environment at admission relates to acute stress disorder symptoms in myocardial infarction patients.

OBJECTIVE Hospital crowding is a public health problem that may impact on the quality of medical treatment and increase the risk of developing traumatic stress, e.g., after myocardial infarction (MI). This study examines whether subjective appraisal of crowding at hospital admission due to MI is associated with acute stress disorder (ASD) symptoms. METHOD We investigated 102 consecutive patients with acute MI within 48h after having reached stable circulatory conditions. The appraisal of crowding was measured by the retrospective assessment of the perception of a hectic hospital environment at admission. Furthermore, patients completed the Acute Stress Disorder Scale to rate the psychological stress reaction. RESULTS The perception of a hectic hospital environment was associated with the development of ASD symptoms (r=0.254, P=.013) independently of demographic, peritraumatic and medical factors. Post hoc analysis revealed associations with dissociative (r=0.211, P=.041), reexperiencing (r=0.184, P=.074) and arousal (r=0.179, P=.083) symptoms. CONCLUSION The findings suggest that, besides objective circumstances, the way hospital admission due to MI is perceived by the patient may influence the development of MI-triggered ASD symptoms. The psychological and physiological long-term outcomes of the perception of a hectic hospital environment and the role of preventive interventions need further examination.

Incremental value of heart-type fatty acid-binding protein in suspected acute myocardial infarction early after symptom onset.

BACKGROUND The early diagnosis of acute myocardial infarction (AMI) very soon after symptom onset remains a major clinical challenge, even when using high-sensitivity cardiac troponin (hs-cTnT). METHODS AND RESULTS We investigated the incremental value of heart-type fatty acid-binding protein (hFABP) in a pre-specified subgroup analysis of patients presenting with suspected AMI within 1 h of symptom onset to the emergency department (ED) in a multicentre study. HFABP was measured in a blinded fashion. Two independent cardiologists using all available clinical information, including hs-cTnT, adjudicated the final diagnosis. Overall, 1411 patients were enrolled, of whom 105 patients presented within 1 h of symptom onset. Of these, 34 patients (32.4%) had AMI. The diagnostic accuracy as quantified by the area under the receiver-operating characteristics curve (AUC) of hFABP was high (0.84 (95% CI 0.74-0.94)). However, the additional use of hFABP only marginally increased the diagnostic accuracy of hs-cTnT (AUC 0.88 (95% CI 0.81-0.94) for hs-cTnT alone to 0.90 (95% CI 0.83-0.98) for the combination; p=ns). After the exclusion of 18 AMI patients with ST-segment elevation, similar results were obtained. Among the 16 AMI patients without ST-segment elevation, six had normal hs-cTnT at presentation. Of these, hFABP was elevated in two (33.3%) patients. CONCLUSIONS hFABP does not seem to significantly improve the early diagnostic accuracy of hs-cTnT in the important subgroup of patients with suspected AMI presenting to the ED very early after symptom onset.

Changes of coronary plaque composition correlate with C-reactive protein levels in patients with ST-elevation myocardial infarction following high-intensity statin therapy.

OBJECTIVES Levels of inflammatory biomarkers associate with changes of coronary atheroma burden in statin-treated patients with stable coronary artery disease. This study sought to determine changes of plaque composition in vivo in relation to high-sensitivity C-reactive protein (hs-CRP) levels in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin therapy. METHODS The IBIS-4 study performed serial (baseline and 13-month), 2-vessel intravascular ultrasound (IVUS) and radiofrequency-IVUS of the non-infarct-related arteries in patients with STEMI treated with high-intensity statin therapy. The present analysis included 44 patients (80 arteries) with serial measurements of hs-CRP. RESULTS At follow-up, median low-density lipoprotein cholesterol (LDL-C) levels decreased from 126 to 77 mg/dl, HDL-C increased from 44 to 47 mg/dl, and hs-CRP decreased from 1.6 to 0.7 mg/L. Regression of percent atheroma volume (-0.99%, 95% CI -1.84 to -0.14, p = 0.024) was accompanied by reduction of percent fibro-fatty (p = 0.04) and fibrous tissue (p < 0.001), and increase in percent necrotic core (p = 0.006) and dense calcium (p < 0.001). Follow-up levels of hs-CRP, but not LDL-C, correlated with changes in percent necrotic core (p = 0.001) and inversely with percent fibrous tissue volume (p = 0.008). Similarly, baseline-to-follow-up change of hs-CRP correlated with the change in percent necrotic core volume (p = 0.02). CONCLUSIONS In STEMI patients receiving high-intensity statin therapy, stabilization of VH-IVUS-defined necrotic core was confined to patients with lowest on-treatment levels and greatest reduction of hs-CRP. Elevated CRP levels at follow-up may identify progression of high-risk coronary plaque composition despite intensive statin therapy and overall regression of atheroma volume.

Decreased phosphatidylcholine plasmalogens - A putative novel lipid signature in patients with stable coronary artery disease and acute myocardial infarction.

OBJECTIVE Glycerophospholipids and sphingolipids are structurally heterogeneous due to differences in the O- and N-linked fatty acids and head groups. Sphingolipids also show a heterogeneity in their sphingoid base composition which up to now has been little appreciated. The aim of this study was to investigate the association of certain glycerophospholipid and sphingolipid species with stable coronary artery disease (CAD) and acute myocardial infarction (AMI). METHODS The lipid profile in plasma from patients with stable CAD (n = 18) or AMI (n = 17) was compared to healthy subjects (n = 14). Sixty five glycerophospholipid and sphingolipid species were quantified by LC-MS. The relative distribution of these lipids into lipoprotein fractions was analyzed. RESULTS In the CAD cohort, 45 glycerophospholipid and sphingolipid species were significantly lower compared to healthy controls. In the AMI group, 42 glycerophospholipid and sphingolipid species were reduced. Four PC plasmalogens (PC33:1, PC33:2, PC33:3 and PC35:3) showed the most significant difference. Out of eleven analyzed sphingoid bases, four were lower in the CAD and six in the AMI group. Sphingosine-1-phosphate (S1P) levels were reduced in the AMI group whereas an atypical C16:1 S1P was lower in both groups. Phosphatidylcholine and sphingomyelin species were exclusively present in lipoprotein particles, whereas lysophosphatidylcholines were mainly found in the lipoprotein-free fraction. The observed differences were not explained by the use of statins as confirmed in a second, independent cohort. CONCLUSIONS Reduced levels of four PC plasmalogens (PC33:1, PC33:2, PC33:3 and PC35:3) were identified as a putatively novel lipid signature for CAD and AMI.

Cryoinjury as a myocardial infarction model for the study of cardiac regeneration in the zebrafish.

The zebrafish heart has the capacity to regenerate after ventricular resection. Although this regeneration model has proved useful for the elucidation of certain regeneration mechanisms, it is based on the removal of heart tissue rather than on tissue damage. We recently characterized the cellular response and regenerative capacity of the zebrafish heart after cryoinjury (CI), an alternative procedure that more closely models the pathophysiological process undergone by the human heart after myocardial infarction (MI). After anesthesia, localized CI with a liquid nitrogen-cooled copper probe induced damage in 25% of the ventricle, in a procedure requiring <5 min. Here we present a detailed description of the technique, which provides a valuable system for the study of the mechanisms of heart regeneration and scar removal after MI in a versatile vertebrate model.

Revascularization Treatment of Emergency Patients with Acute ST-Segment Elevation Myocardial Infarction in Switzerland: Results from a Nationwide, Cross-Sectional Study in Switzerland for 2010-2011

BACKGROUND: Cardiovascular diseases are the leading cause of death worldwide and in Switzerland. When applied, treatment guidelines for patients with acute ST-segment elevation myocardial infarction (STEMI) improve the clinical outcome and should eliminate treatment differences by sex and age for patients whose clinical situations are identical. In Switzerland, the rate at which STEMI patients receive revascularization may vary by patient and hospital characteristics. AIMS: To examine all hospitalizations in Switzerland from 2010-2011 to determine if patient or hospital characteristics affected the rate of revascularization (receiving either a percutaneous coronary intervention or a coronary artery bypass grafting) in acute STEMI patients. DATA AND METHODS: We used national data sets on hospital stays, and on hospital infrastructure and operating characteristics, for the years 2010 and 2011, to identify all emergency patients admitted with the main diagnosis of acute STEMI. We then calculated the proportion of patients who were treated with revascularization. We used multivariable multilevel Poisson regression to determine if receipt of revascularization varied by patient and hospital characteristics. RESULTS: Of the 9,696 cases we identified, 71.6% received revascularization. Patients were less likely to receive revascularization if they were female, and 80 years or older. In the multivariable multilevel Poisson regression analysis, there was a trend for small-volume hospitals performing fewer revascularizations but this was not statistically significant while being female (Relative Proportion = 0.91, 95% CI: 0.86 to 0.97) and being older than 80 years was still associated with less frequent revascularization. CONCLUSION: Female and older patients were less likely to receive revascularization. Further research needs to clarify whether this reflects differential application of treatment guidelines or limitations in this kind of routine data.