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Summary In this report, we describe the first chronic case of Q fever endocarditis in a 72-year-old woman in Iran. The patient developed radiation-associated heart disease status post (s/p) coronary artery bypass surgery, mitral and aortic valve replacements, and tricuspid valve repair. Endocarditis was also suspected due to a history of heart valve surgery. Blood cultures were negative, but a diagnosis of Q fever endocarditis was confirmed based on serologic titers (IgG phase I 1:32,768). The patient was treated with doxycycline and hydroxychloroquine. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to determine feasibility and prognostic performance of stress cardiac magnetic resonance (CMR) in obese patients (body mass index [BMI] ≥30 kg/m2). Background: Current stress imaging methods remain limited in obese patients. Given the impact of the obesity epidemic on cardiovascular disease, alternative methods to effectively risk stratify obese patients are needed. Methods: Consecutive patients with a BMI ≥30 kg/m2 referred for vasodilating stress CMR were followed for major adverse cardiovascular events (MACE), defined as cardiac death or nonfatal myocardial infarction. Univariable and multivariable Cox regressions for MACE were performed to determine the prognostic association of inducible ischemia or late gadolinium enhancement (LGE) by CMR beyond traditional clinical risk indexes. Results: Of 285 obese patients, 272 (95%) completed the CMR protocol, and among these, 255 (94%) achieved diagnostic imaging quality. Mean BMI was 35.4 ± 4.8 kg/m2, with a maximum weight of 200 kg. Reasons for failure to complete CMR included claustrophobia (n = 4), intolerance to stress agent (n = 4), poor gating (n = 4), and declining participation (n = 1). Sedation was required in 19 patients (7%; 2 patients with intravenous sedation). Sixteen patients required scanning by a 70-cm–bore system (6%). Patients without inducible ischemia or LGE experienced a substantially lower annual rate of MACE (0.3% vs. 6.3% for those with ischemia and 6.7% for those with ischemia and LGE). Median follow-up of the cohort was 2.1 years. In a multivariable stepwise Cox regression including clinical characteristics and CMR indexes, inducible ischemia (hazard ratio 7.5; 95% confidence interval: 2.0 to 28.0; p = 0.002) remained independently associated with MACE. When patients with early coronary revascularization (within 90 days of CMR) were censored on the day of revascularization, both presence of inducible ischemia and ischemia extent per segment maintained a strong association with MACE. Conclusions: Stress CMR is feasible and effective in prognosticating obese patients, with a very low negative event rate in patients without ischemia or infarction. [Copyright &y& Elsevier]

With the need for healthcare cost-containment, increased scrutiny will be placed on new medical therapeutic or diagnostic technologies. Several challenges exist for a new diagnostic test to demonstrate cost-effectiveness. New diagnostic tests differ from therapeutic procedures due to the fact that diagnostic tests do not generally directly affect long-term patient outcomes. Instead, the results of diagnostic tests can influence management decisions for patients and by this route, diagnostic tests indirectly affect long-term outcomes. The benefits from a specific diagnostic technology depend therefore not only on its performance characteristics, but also on other factors such as prevalence of disease, and effectiveness of existing treatments for the disease of interest. We review the concepts and theories of cost-effectiveness analyses (CEA) as they apply to diagnostic tests in general. The limitations of CEA across different study designs and geographic regions are discussed, and we also examine the strengths and weakness of the existing publications where CMR was the focus of CEA compared to other diagnostic options. [ABSTRACT FROM AUTHOR]

Objectives: The major aim of this study is to test the hypothesis that stress cardiac magnetic resonance (CMR) imaging can provide robust prognostic value in women presenting with suspected ischemia, to the same extent as in men. Background: Compelling evidence indicates that women with coronary artery disease (CAD) experience worse outcomes than men owing to a lack of early diagnosis and management. Numerous clinical studies have shown that stress CMR detects evidence of myocardial ischemia and infarction at high accuracy. Compared to nuclear scintigraphy, CMR is free of ionizing radiation, has high spatial resolution for imaging small hearts, and overcomes breast attenuation artifacts, which are substantial advantages when imaging women for CAD. Methods: We performed stress CMR in 405 patients (168 women, mean age 58 ± 14 years) referred for ischemia assessment. CMR techniques included cine cardiac function, perfusion imaging during vasodilating stress, and late gadolinium enhancement imaging. All patients were followed for major adverse cardiac events (MACE). Results: At a median follow-up of 30 months, MACE occurred in 36 patients (9%) including 21 cardiac deaths and 15 acute myocardial infarctions. In women, CMR evidence of ischemia (ISCHEMIA) demonstrated strong association with MACE (unadjusted hazard ratio: 49.9, p < 0.0001). While women with ISCHEMIA(+) had an annual MACE rate of 15%, women with ISCHEMIA(−) had very low annual MACE rate (0.3%), which was not statistically different from the low annual MACE rate in men with ISCHEMIA(−) (1.1%). CMR myocardial ischemia score was the strongest multivariable predictor of MACE in this cohort, for both women and men, indicating robust cardiac prognostication regardless of sex. Conclusions: In addition to avoiding exposure to ionizing radiation, stress CMR myocardial perfusion imaging is an effective and robust risk-stratifying tool for patients of either sex presenting with possible ischemia. [Copyright &y& Elsevier]

Abstract: There have been tremendous technological advances in noninvasive cardiovascular imaging, offering the clinician unparalleled information from a variety of modalities. Cardiovascular magnetic resonance imaging (MRI) has the advantages of superior spatial resolution, detailed tissue characterization, and accurate quantitative assessment of cardiac structure and function, without the need for radiation exposure. Recent advances in image acquisition and postimage processing have led to clinically validated protocols for myocardial perfusion, late gadolinium enhancement, and coronary angiography. The following collection of images was selected to demonstrate the typical appearance of various cardiovascular conditions using MRI. There is, of course, much heterogeneity in both the phenotypic severity of a given condition as well as its appearance on MRI. This article, while not intended to be a comprehensive collection, aims to serve as an introduction to the current applications of cardiac MRI. [Copyright &y& Elsevier]

Rho GTPases control fundamental cellular processes, including cytoskeletal reorganization and transcription. Rho guanine nucleotide exchange factors (GEFs) compose a large (>65) and diverse family of related proteins that activate Rho GTPases. Lsc/p115-RhoGEF is a Rho-specific GEF required for normal B and T lymphocyte function. Despite its essential role in lymphocytes, Lsc/p115-RhoGEF signaling in vivo is not well understood. To define Lsc/p115-RhoGEF signaling pathways in vivo, we set out to identify proteins that interact with regulatory regions of Lsc. The 146-amino acid C terminus of Lsc contains a predicted coiled-coil domain, and we demonstrated that deletion of this C terminus confers a gain of function in vivo. Surprisingly, a yeast two-hybrid screen for proteins that interact with this regulatory C terminus isolated a larger C-terminal fragment of Lsc itself. Co-immunoprecipitation experiments in mammalian cells demonstrated that Lsc specifically homo-oligomerizes and that the coiled-coil domain in the C terminus is required for homo-oligomerization. Mutagenesis experiments revealed that homo-oligomerization and negative regulation are distinct functions of the C terminus. Two novel isoforms of Lsc found in the spleen lack portions of this C terminus, including the coiled-coil domain. Importantly, the C termini of both isoforms confer a gain of function and eliminate homooligomerization. These results define two important features of Lsc signaling. First, Lsc homo-oligomerizes and is negatively regulated through domains in its C terminus; and second, functionally distinct isoforms of Lsc lacking these domains are present in the spleen. [ABSTRACT FROM AUTHOR]

An abstract of the article "Diabetes remains an independent risk factor for adverse remodeling following acute myocardial infarction even with quantification of total infarct size and change in myocardial extracellular volume fraction by CMR," by Bobby Heydari and colleagues is presented.

An abstract of the conference paper "Stress CMR myocardial perfusion imaging (CMR-MPI) is cost-effective compared to nuclear SPECT: a retrospective cost-effectiveness analysis," by Sanjeev Francis and colleagues is presented.

An abstract of a conference paper related to characterization of fibrotic burden in the remote myocardium after acute infarction which helps in prediction of changes in functions by Damien Mandry and colleagues is presented.

An abstract of a conference paper related to CMR quantification of infarct tissue heterogeneity and remote myocardial fibrotic burden during convalescent phase following acute myocardial infarction by Bobby Heydari and colleagues is presented.

Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocarditis) may present similarly and/or overlap with other cardiac pathology including acute coronary syndrome presenting a challenge for prompt clinical diagnosis. An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery stenosis >70% in patients undergoing coronary angiogram. Among 261 patients with clinically suspected ICB-myocarditis who underwent a coronary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coronary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revascularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84–8.84, p < 0.001) and was marginally associated with all-cause death (HR = 1.88, 95% CI, 0.98–3.61, p = 0.057). CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diagnosis and treatment or more severe presentation of ICB-myocarditis. • ICB-myocarditis can clinically present similarly to acute coronary syndrome. • Diagnostic steps are similar; treatment of both entities is substantially different. • Delay in appropriate treatments of severe ICB-myocarditis should be avoided. [ABSTRACT FROM AUTHOR]

Anthracyclines are an important component of cancer treatments; however, their use is limited by the occurrence of cardiotoxicity. There are limited data on the occurrence of heart failure and the value of baseline and follow-up measurements of left ventricular (LV) ejection fraction (EF) in the current era. Therefore, the objectives of the present study were twofold: (1) to characterize the occurrence of and risk factors for major adverse cardiac events (MACEs: symptomatic heart failure and cardiac death) in a large contemporaneous population of adult patients treated with anthracyclines and (2) to test the value of LVEF and LV dimensions obtained using echocardiography in the prediction of MACE. Five thousand fifty-seven patients were studied, of whom 124 (2.4%) developed MACE. Of the total cohort, 2,285 patients had an available echocardiogram pre-chemotherapy. Patients with MACE were older (p <0.0001), predominantly men (p = 0.03), and with a higher incidence of cardiovascular risk factors and cardiac treatments. Patients with hematologic cancers had a higher incidence of cardiac events than patients with breast cancer (4.2% vs 0.7%, p <0.0001). Baseline LVEF, LVEF ≤5 points above the lower limits of normal, and LV internal diameter were predictive of the rate of occurrence of MACE. In conclusion, older patients with hematologic cancers and patients with a baseline LVEF ≤5 points above the lower limit of normal have higher incidence of MACE and should be closely monitored. [ABSTRACT FROM AUTHOR]

We aimed to determine whether the myocardial extracellular volume (ECV), measured using T1 measurements obtained during cardiac magnetic resonance imaging were increased in patients treated with anthracyclines. We performed cardiac magnetic resonance imaging and echocardiography and measured the ECV in 42 patients treated with anthracyclines. The data from the cardiac magnetic resonance study were compared to those from healthy volunteers. The anthracycline-treated cohort consisted of 21 men and 21 women with a mean age of 55 ± 17 years, who presented a median of 84 months after chemotherapy with a cumulative anthracycline exposure of 282 ± 65 mg/m² and a mean left ventricular ejection fraction of 52 ± 12%. The ECV was elevated in the anthracyclinetreated patients compared to the age- and gender-matched controls (0.36 ± 0.03 vs 0.28 ± 0.02, p <0.001). A positive association was found between the ECV and left atrial volume (ECV vs indexed left atrial volume, r = 0.65, p <0.001), and negative association was found between the ECV and diastolic function (E' lateral, r = -0.64, p <0.001). In conclusion, the myocardial ECV is elevated in patients with previous anthracycline treatment and is associated with the diastolic function and increased atrial volumes. [ABSTRACT FROM AUTHOR]

We aimed to describe the cardiac magnetic resonance (CMR) findings and determine the prognostic variables in patients with a cardiomyopathy after treatment with anthracyclines. CMR imaging was performed in 91 patients (58% men, mean age 43 ± 18 years, and mean anthracycline dose of 276 ± 82 mg/m2) with a reduced ejection fraction after anthracycline-based chemotherapy. Major adverse cardiovascular events were defined as cardiovascular death, appropriate implantable cardioverter-defibrillator therapy, and admission for decompensated heart failure. Patients presented a median of 88 months (interquartile range 37 to 138) after chemotherapy and were followed for 27 months (interquartile range 22 to 38). Late gadolinium enhancement was an uncommon finding (5 patients, 6%) despite a reduced ejection fraction (36 ± 8%). An inverse association was found between the anthracycline dose and the indexed left ventricular (LV) mass by CMR (r = −0.67, p <0.001). A total of 52 adverse cardiac events occurred (event rate of 22%/year). When the patients were grouped according to the presence or absence of a major adverse cardiovascular event, the indexed LV mass and glomerular filtration rate were lower and the anthracycline dose was greater among the patients who experienced an adverse event. In a multivariate model, the indexed LV mass demonstrated the strongest association with major adverse cardiovascular events (hazard ratio 0.89, chi-square 26, p <0.001). In conclusion, myocardial scar by late gadolinium enhancement-CMR is infrequent in patients with anthracycline-cardiomyopathy despite a reduced ejection fraction, the event rate in patients with established anthracycline-cardiotoxicity is high, and indexed LV mass by CMR imaging is a predictor of adverse cardiovascular events. [Copyright &y& Elsevier]

Cysteinyl leukotrienes (cys-LT5) are potent inflammatory lipid mediators, of which leukotriene (LT) E4 is the most stable and abundant in vivo. Although only a weak agonist of established G protein-coupled receptors (GPCRs) for cys-LTs, LTE4 potentiates airway hyper-responsiveness (AHR) by a cyclooxy-genase (COX)-dependent mechanism and induces bronchial eosinophilia. We now report that LTE4 activates human mast cells (MCs) by a pathway involving cooperation between an MK571-sensitive GPCR and peroxisome proliferator-activated receptor (PPAR)γ, a nuclear receptor for dietary lipids. Although LTD4 is more potent than LTE4 for inducing calcium flux by the human MC sarcoma line LAD2, LTE4 is more potent for inducing proliferation and chemokine generation, and is at least as potent for upregulating COX-2 expression and causing prostaglandin D2 (PGD2) generation. LTE4 caused phosphorylation of extracellular signal-regulated kinase (ERK), p9ORSK, and cyclic AMP-regulated-binding protein (CREB). ERK activation in response to LTE4, but not to LTD4, was resistant to inhibitors of phosphoinositol 3-kinase. LTE4-mediated COX-2 induction, PGD2 generation, and ERK phosphorylation were all sensitive to interference by the PPARy antagonist GW9662 and to targeted knockdown of PPARγ. Although LTE4-mediated PGD2 production was also sensitive to MK571, an antagonist for the type 1 receptor for cys-LTs (CysLT1R), it was resistant to knockdown of this receptor. This LTE4-selective receptor-mediated pathway may explain the unique physiologic responses of human airways to LTE4 in vivo. [ABSTRACT FROM AUTHOR]