Coronary artery calcium scores (CACS) from lung cancer screening computed tomography (LCSCT) or myocardial perfusion attenuation correction computed tomography (ACCT) are not routinely performed or reported. CACS from LCSCT and ACCT have not been directly compared in the same patient population. We identified 66 patients who underwent both LCSCT (non-gated) and ECG-gated cardiac CT (CCT) within a 2-year span. Of this population, 40 subjects had also undergone ACCT. Using the Agatston method, CACS for 264 individual vessels from the LCSCT population and for 160 vessels from ACCT population were calculated and evaluated for agreement with ECG-gated CCT as the gold standard. Secondary analysis included a comparison of individual vessel contribution to variations in agreement and a comparison of total CACS from CCT, LCSCT, and ACCT for respective MACE prediction. CACS from LCSCT demonstrated a strong Pearson correlation, r = 0.9017 (0.876-0.9223), with good agreement when compared to CACS from CCT. CACS from ACCT demonstrated a significantly (P < 0.00001) weaker correlation, r = 0.5593 (0.4401-0.6592). On an individual vessel basis, CACS from all major vessels (LM, LAD, LCX, and RCA) contributed to the weaker correlation. For total vessel CACS, LCSCT demonstrated comparable area under the curve (AUC) for the receiver operating characteristic (ROC) curve (LCSCT AUC = 0.8133 and CCT AUC = 0.8302, P = 0.691) for prediction of MACE. Although ACCT demonstrated a similar AUC (ACCT AUC = 0.7969, P = 0.662) for MACE prediction the cutoff value for elevated risk was extremely low. In conclusion, LCSCT outperformed ACCT at calcium scoring by providing better agreement and comparable risk assessment to CCT despite the absence of ECG-gating. It is therefore reasonable to use LCSCT images to derive and report Agatston-based CACS for cardiovascular risk assessment, whereas the use of ACCT images to report Agatston-based CACS is not currently practical.

Coronary artery disease caused by atherosclerosis is the leading cause of morbidity and mortality in the world. Calcification of atherosclerotic plaque has predictive value in terms of cardiovascular event risk and mortality. The composition of calcium within plaque ( i.e. increased calcium density) has been associated with reduced vulnerability for cardiac events. Therapeutic modulation of atherosclerotic plaque calcium composition may have tremendous potential in terms of reducing event risk. HMG-CoA reductase inhibitors (statins) are a well-established family of medications that reduce the risk of myocardial infarction and are associated with increased plaque calcification, yet the underlying mechanisms of these processes are not well understood. Moreover, statin use can be associated with significant adverse reactions ( i.e. myalgias and new onset diabetes). Our group has identified a Rac-dependent inflammatory pathway that promotes IL-1β-driven atherosclerotic calcification. Using an atherosclerotic-prone mouse model, we found that progressive calcification of atherosclerotic plaque depends on altered Rac signaling and consequent IL-1β expression. Statin-treated primary macrophages expressed higher IL-1β mRNA and secreted more IL-1β protein in response to inflammasome activation by TLR-coupled cholesterol crystal phagocytosis. This statin-induced augmentation of IL-1β production depended on Rac1, as small molecule inhibition of Rac1 and Rac1 gene-deletion abrogated this effect. Statin treatment disrupted the association of Rac1 with its native inhibitor, Rho-GDI, through loss of Rac1 isoprenylation, and as a consequence, statin-treated macrophages demonstrated higher levels of GTP-bound Rac1. This higher activation of Rac1 led to increased NF-κB activation and consequent macrophage IL-1β mRNA expression. ApoE -/- mice placed on high fat diet with statin therapy revealed increases in aortic plaque calcification relative to control mice in association with altered serum IL-1β levels. Defining Rac signaling as a key mediator of statin-dependent mechanisms that modulate plaque calcium composition and consequent plaque stability may lead to novel therapeutic strategies for the prevention of cardiovascular events.

Acute ST-segment elevation myocardial infarction is a medical emergency requiring prompt recognition of the syndrome and initiation of reperfusion therapy. The usual pathophysiologic mechanism of transmural myocardial injury is acute thrombotic occlusion of an epicardial coronary artery. Other conditions can masquerade as ST-elevation myocardial infarction with different mechanisms of myocardial injury. We report a case of eosinophilic myocarditis manifesting as acute ST-segment elevation myocardial infarction in the setting of chronic idiopathic hypereosinophilia diagnosed using cardiac magnetic resonance imaging. A 60-year-old gentleman with a history of chronic obstructive pulmonary disease and hypertension was referred to the Emergency Department by his hematologist for further work-up of new-onset arthralgias, leukocytosis (23,000 cells/μL) with eosinophilia (41%), and elevated erythrocyte sedimentation rate (51 mm/h). He had been referred to a hematologist after a recent hospitalization with splenic infarcts, leukocytosis, and eosinophilia of unclear etiology. Further review of his records demonstrated eosinophilia as far back as 18 months before admission. During his previous admission, an extensive work-up including anticardiolipin antibody, beta-2 glycoprotein, antinuclear antibody, JAK2 mutation, FIP1L-PDGfRA, lupus anticoagulant, tryptase and bcr/abl, anti scl-70, antineutrophil cytoplasmic antibodies, anticyclic citrullinated peptide antibody, rheumatoid factor, flow cytometry, karyotyping, stool ova and parasites, and strongyloides, was negative. A bone marrow biopsy demonstrated significant eosinophilia, suggesting a hypereosinophilic state. He was admitted to our hospital for further evaluation and management. On day 1 of his hospitalization, he developed sudden-onset retrosternal chest pain while lying in bed. Electrocardiogram showed 3-mm ST-segment elevation in leads II, III, and AVF (Figure 1). Troponin I was elevated to 0.536 ng/mL. He was administered aspirin, clopidogrel, metoprolol, and atorvastatin, and started on an intravenous heparin infusion. A bedside transthoracic echocardiogram showed hypokinesis of the inferolateral and anterolateral segments, which were new compared with a previous echocardiogram (Figure 2). Urgent coronary angiography demonstrated mild nonobstructive coronary disease (Figure 3). He subsequently underwent cardiac magnetic resonance imaging using a Philips 3T scanner (Philips Healthcare, Andover, MA) with gadolinium contrast that was administered (0.2 mmol/kg) with images taken after a delay of 10 minutes. This demonstrated multiple noncontiguous focal areas of late gadolinium enhancement, including transmural and epicardial areas, with corresponding wall motion abnormalities, suggestive of infiltrative myocarditis (Figure 4).Figure 2Transthoracic echocardiogram apical 4-chamber views in diastole (A) and systole (B) showing hypokinesis of the mid-inferoseptum (arrows).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Coronary angiograms demonstrating normal left (A) and right (B) coronary arteries.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 4Cardiac magnetic resonance imaging 4-chamber (A) and short-axis (B) views demonstrating noncontiguous focal areas of late gadolinium enhancement in the mid septum and inferolateral walls.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Hypereosinophilia is a syndrome whose hallmark feature is overproduction of eosinophils, defined as having an absolute eosinophil count of >1.5 × 109/L (1500/μL) on 2 separate occasions.1Chusid M.J. Dale D.C. West B.C. et al.The hypereosinophilic syndrome. Analysis of fourteen cases with review of the literature.Medicine (Baltimore). 1975; 54: 1-27Crossref PubMed Scopus (1196) Google Scholar This is often noted incidentally on routine blood work, and the cause is not immediately obvious. A hypereosinophilic syndrome is diagnosed when there is evidence of end-organ damage from eosinophilic tissue infiltration with resultant oxidative and enzymatic injury.2Weller P.F. Bubley G.J. The idiopathic hypereosinophilic syndrome.Blood. 1994; 83: 2759-2779PubMed Google Scholar, 3Tai P.C. Ackerman S.J. Spry C.J. et al.Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease.Lancet. 1987; 1: 643-647Abstract PubMed Scopus (244) Google Scholar Myocardial involvement is common, occurring in upwards of 60% of patients with hypereosinophilic syndrome, and is now a major cause of morbidity and mortality if not treated appropriately.4ten Oever J. Theunissen L.J. Tick L.W. Verbunt R.J. Cardiac involvement in hypereosinophilic syndrome.Neth J Med. 2011; 69: 240-243PubMed Google Scholar, 5Kleinfeldt T. Nienaber C.A. Kische S. et al.Cardiac manifestation of the hypereosinophilic syndrome: new insights.Clin Res Cardiol. 2010; 99: 419-427Crossref PubMed Scopus (66) Google Scholar, 6Al Ali A.M. Straatman L.P. Allard M.F. Ignaszewski A.P. Eosinophilic myocarditis: case series and review of literature.Can J Cardiol. 2006; 22: 1233-1237Abstract Full Text PDF PubMed Scopus (98) Google Scholar The association between eosinophilia and cardiac injury was first described by Löffler in 1936,7Löffler W. Schweiz Med Wochenschr. 1936; 18 ([German]): 817-820Google Scholar initially as fibroplastic endocarditis or Loeffler's endocarditis. He proposed that eosinophilic infiltration of the endocardium with resultant fibrosis was the mechanism of injury resulting in constrictive physiology and severe heart failure. Myocardial injury as a result of eosinophilic infiltration involves recruitment of eosinophils into the myocardial tissue with toxic degranulation.3Tai P.C. Ackerman S.J. Spry C.J. et al.Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease.Lancet. 1987; 1: 643-647Abstract PubMed Scopus (244) Google Scholar The current understanding of eosinophilic myocarditis describes a 3-stage process of myocardial injury.4ten Oever J. Theunissen L.J. Tick L.W. Verbunt R.J. Cardiac involvement in hypereosinophilic syndrome.Neth J Med. 2011; 69: 240-243PubMed Google Scholar, 5Kleinfeldt T. Nienaber C.A. Kische S. et al.Cardiac manifestation of the hypereosinophilic syndrome: new insights.Clin Res Cardiol. 2010; 99: 419-427Crossref PubMed Scopus (66) Google Scholar, 8Take M. Sekiguchi M. Hiroe M. et al.Clinical spectrum and endomyocardial biopsy findings in eosinophilic heart disease.Heart Vessels Suppl. 1985; 1: 243-249Crossref PubMed Scopus (23) Google Scholar, 9Fredy F. Iskandar W. Jih F. Cardiac involvement mimicking acute coronary syndrome in idiopathic hypereosinophilic syndrome.Acta Med Indones. 2013; 45: 302-305PubMed Google Scholar, 10Houman R. Sanchez-Ross M. Kaluski E. Klapholz M. Haider B. Gerula C. Acute eosinophilic myocarditis: diagnosis and treatment.Acute Cardiac Care. 2010; 12: 31-36Crossref PubMed Scopus (30) Google Scholar The first stage is the acute necrotic phase, which involves myocardial infiltration with eosinophils and toxic degranulation, resulting in myocardial injury. This stage is typically subclinical and patients are often asymptomatic. The second stage is the thrombotic phase, involving thrombus formation on the endocardial surface. Symptoms often first appear during this stage due to thromboembolic events. This was the case with our patient, who had initially presented with splenic infarcts. The final stage is a fibrotic phase, where scar replaces the injured myocardium, resulting in endomyocardial fibrosis, which may lead to a restrictive cardiomyopathy and congestive heart failure. Combinations of fibrosis and inflammation can be seen across a continuum in the latter 2 stages. There are few reported cases of ST-segment elevation myocardial infarction as the presenting feature of patients with eosinophilic myocarditis.11Amini R. Nielsen C. Eosinophilic myocarditis mimicking acute coronary syndrome secondary to idiopathic hypereosinophilic syndrome: a case report.J Med Case Rep. 2010; 4: 40Crossref PubMed Scopus (23) Google Scholar, 12Enriquez A. Castro P. Gabrielli L. et al.Acute necrotizing eosinophilic myocarditis presenting as ST-elevation myocardial infarction: a case report.Can J Cardiol. 2011; 27: 870.e1-870.e3Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar, 13Takahasi N. Kondo K. Aoyagi J. Acute myocardial infarction associated with hypereosinophilic syndrome in a young man.Jpn Circ J. 1997; 61: 803-806Crossref PubMed Scopus (16) Google Scholar Endomyocardial biopsy (EMB) has historically been the gold standard for diagnosis of cardiac eosinophilic infiltration. However, due to the noncontiguous and patchy nature of eosinophilic infiltration, EMB may miss active areas of infiltration, resulting in a false negative and delaying diagnosis. Furthermore, EMB is an invasive procedure with the potential for serious complications, including cardiac perforation, conduction abnormalities, and pericardial effusion.14Holzmann M. Nicko A. Kühl U. et al.Complication rate of right ventricular endomyocardial biopsy via the femoral approach: a retrospective and prospective study analyzing 3048 diagnostic procedures over an 11-year period.Circulation. 2008; 118: 1722-1728Crossref PubMed Scopus (196) Google Scholar Cardiac magnetic resonance (CMR) imaging performed with gadolinium contrast enhancement can detect even early-stage cardiac involvement and can distinguish among the 3 stages.4ten Oever J. Theunissen L.J. Tick L.W. Verbunt R.J. Cardiac involvement in hypereosinophilic syndrome.Neth J Med. 2011; 69: 240-243PubMed Google Scholar, 15Debl K. Djavidani B. Buchner S. et al.Time course of eosinophilic myocarditis visualized by CMR.J Cardiovasc Magn Reson. 2008; 10: 20-21Crossref PubMed Scopus (21) Google Scholar, 16Kim Y. Chang S. Lee Y. Choi J. Hyeon Y. Early non-invasive diagnosis and treatment of acute eosinophlic myopericarditis by cardiac magnetic resonance.J Korean Med Sci. 2011; 26: 1522-1526Crossref PubMed Scopus (11) Google Scholar, 17Syed I. Martinez M. Feng D. Glockner J. Cardiac magnetic resonance imaging of eosinophilic endomyocardial disease.Int J Cardiol. 2008; 126: e50-e52Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar During the first stage, CMR can detect necrosis and inflammation through sub-endocardial late gadolinium enhancement. In the second and third stages of eosinophilic myocarditis, CMR can visualize thrombi as well as areas of myocardial inflammation and fibrosis. Thrombi appear as hypointense areas overlying the endocardium, whereas inflammation and fibrosis are both hyper-enhanced lesions.4ten Oever J. Theunissen L.J. Tick L.W. Verbunt R.J. Cardiac involvement in hypereosinophilic syndrome.Neth J Med. 2011; 69: 240-243PubMed Google Scholar, 17Syed I. Martinez M. Feng D. Glockner J. Cardiac magnetic resonance imaging of eosinophilic endomyocardial disease.Int J Cardiol. 2008; 126: e50-e52Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar

Calcification of atherosclerotic lesions was long thought to be an age - related, passive process, but increasingly data has revealed that atherosclerotic calcification is a more active process, involving complex signaling pathways and bone-like genetic programs. Initially, imaging of atherosclerotic calcification was limited to gross assessment of calcium burden, which is associated with total atherosclerotic burden and risk of cardiovascular mortality and of all cause mortality. More recently, sophisticated molecular imaging studies of the various processes involved in calcification have begun to elucidate information about plaque calcium composition and consequent vulnerability to rupture, leading to hard cardiovascular events like myocardial infarction. As such, there has been renewed interest in imaging calcification to advance risk assessment accuracy in an evolving era of precision medicine. Here we summarize recent advances in our understanding of the biologic process of atherosclerotic calcification as well as some of the molecular imaging tools used to assess it.

BACKGROUND:Practice-based learning and improvement is one of the Accreditation Council of Graduate Medical Education's core competencies fortrainees. Residencyprograms have grappled with how to accomplish this goal.AIM:We describe our institution's unique, longitudinal post-graduate year process and project.SETTING:West Haven, VA Medical Center.PARTICIPANTS:Yale University School of Medicine junior residents on ambulatory electives and faculty preceptor.PROGRAM DESCRIPTION:Longitudinal program aimed to decrease re-admissions for hospitalized patients with congestive heart failure.DISCUSSION:We feel that our longitudinal project is a novel innovation worthy of further study.