Initial 320-detector row coronary CT images have consistently excellent quality and iodinated contrast opacification. These patients were scanned with conservative protocols with respect to iodine load, prospective ECG-gating phase window, and craniocaudal coverage. Future work will focus on lowering contrast and radiation dose while maintaining image quality.
Background-Silent myocardial infarctions (MIs) are prevalent among diabetic patients and inflict significant morbidity and mortality. Although late gadolinium enhancement (LGE) imaging by cardiac magnetic resonance (CMR) can provide sensitive characterization of myocardial scar, its prognostic significance in diabetic patients without any clinical evidence of MI is unknown. Methods and Results-We performed clinically indicated CMR imaging in 187 diabetic patients who were grouped by the absence (study group, nϭ109) or presence (control group, nϭ78) of clinical evidence of MI (clinical history of MI or Q waves on ECG). CMR imaging and follow-up were successful in 107 study patients (98%) and 74 control patients (95%). Cox regression analyses were performed to associate LGE with major adverse cardiovascular events (MACE), including death, acute MI, new congestive heart failure or unstable angina, stroke, and significant ventricular arrhythmias.LGE by CMR was present in 30 of 107 study patients (28%). At a median follow-up of 17 months, 38 of 107 patients (36%) experienced MACE, which included 18 deaths. Presence of LGE was associated with a Ͼ3-fold hazards increase for MACE and for death (hazard ratio, 3.71 and 3.61; PϽ0.001 and Pϭ0.007, respectively). Adjusted to a model that combines patient age, sex, ST or T changes on ECG, and left ventricular end-systolic volume index, LGE maintained a Ͼ4-fold hazards increase for MACE (adjusted hazard ratio, 4.13; 95% confidence interval, 1.74 to 9.79; Pϭ0.001). In addition, LGE provided significant prognostic value with MACE and with death adjusted to a diabetic-specific risk model for 5-year events. The presence of LGE was the strongest multivariable predictor of MACE and death by stepwise selection in the study patients. Conclusions-CMR imaging can characterize occult myocardial scar consistent with MI in diabetic patients without clinical evidence of MI. This imaging finding demonstrates strong association with MACE and mortality hazards that is incremental to clinical, ECG, and left ventricular function combined.
Rationale: Excess signaling through cardiac G␥ subunits is an important component of heart failure (HF) pathophysiology. They recruit elevated levels of cytosolic G protein-coupled receptor kinase (GRK)2 to agonist-stimulated -adrenergic receptors (-ARs) in HF, leading to chronic -AR desensitization and downregulation; these events are all hallmarks of HF. Previous data suggested that inhibiting G␥ signaling and its interaction with GRK2 could be of therapeutic value in HF. Objective: We sought to investigate small molecule G␥ inhibition in HF. Methods and Results: We recently described novel small molecule G␥ inhibitors that selectively block G␥-binding interactions, including M119 and its highly related analog, gallein. These compounds blocked interaction of G␥ and GRK2 in vitro and in HL60 cells. Here, we show they reduced -AR-mediated membrane recruitment of GRK2 in isolated adult mouse cardiomyocytes. Furthermore, M119 enhanced both adenylyl cyclase activity and cardiomyocyte contractility in response to -AR agonist. To evaluate their cardiac-specific effects in vivo, we initially used an acute pharmacological HF model (30 mg/kg per day isoproterenol, 7 days). Concurrent daily injections prevented HF and partially normalized cardiac morphology and GRK2 expression in this acute HF model. To investigate possible efficacy in halting progression of preexisting HF, calsequestrin cardiac transgenic mice (CSQ) with extant HF received daily injections for 28 days. The compound alone halted HF progression and partially normalized heart size, morphology, and cardiac expression of HF marker genes (GRK2, atrial natriuretic factor, and -myosin heavy chain). Conclusions: These data suggest a promising therapeutic role for small molecule inhibition of pathological G␥ signaling in the treatment of HF. (Circ Res. 2010;107:532-539.)Key Words: G proteins Ⅲ adrenergic receptor Ⅲ G protein-coupled receptor kinases Ⅲ cardiomyopathy Ⅲ heart failure Ⅲ cardiomyocyte H eart failure (HF) is a devastating disease with poor prognosis, and remains a leading cause of death worldwide. 1,2 Excess signaling through cardiac G protein G␥ subunits is an important component of HF pathophysiology. In particular, they recruit elevated levels of cytosolic G protein-coupled receptor kinase 2 (GRK2) (-adrenergic receptor kinase [-ARK]1) to agonist-stimulated -ARs in HF, 3 leading to the chronic -AR desensitization, downregulation and pathological signaling that are hallmarks of HF. 4,5 Increasing evidence suggests a critical role for G␥-mediated signaling in HF. In particular, GRK2 is significantly upregulated in cardiomyocytes of animal models of HF and human HF patients; this elevates G␥-GRK2 interactions and contributes to chronic desensitization of -AR signaling 6,7 ; interestingly, levels of GRK2 appear to correlate with the severity of HF. 6,8 Enhancing G␥-GRK2 interaction by cardiac targeted overexpression of GRK2(s) can directly cause HF in experimental animal models 9 ; its genetic ablation has generally proven to be...
Cardiac amyloidosis in the United States is most often due to myocardial infiltration by immunoglobulin protein, such as in AL amyloidosis, or by the protein transthyretin, such as in hereditary and senile amyloidosis. Cardiac amyloidosis often portends a poor prognosis especially in patients with systemic AL amyloidosis. Despite better understanding of the pathophysiology of amyloid, many patients are still diagnosed late in the disease course. This review investigates the current understanding and new research on the diagnosis and treatment strategies in patients with cardiac amyloidosis. Myocardial amyloid infiltration distribution occurs in a variety of patterns. Structural and functional changes on echocardiography can suggest presence of amyloid, but CMR and nuclear imaging provide important complementary information on amyloid burden and the amyloid subtype, respectively. While for AL amyloid, treatment success largely depends on early diagnosis, for ATTR amyloid, new investigational agents that reduce production of transthyretin protein may have significant impact on clinical outcomes. Advancements in the non-invasive diagnostic detection and improvements in early disease recognition will undoubtedly facilitate a larger proportion of patients to receive early therapy when it is most effective.
Significant regional differences exist for mean left atrial wall thickness among the different anatomic areas within the left atrium which are often targeted during catheter ablation of AF. These differences may have significant implications in determining the ideal intensity and total duration of radiofrequency energy required to achieve a safe and successful ablation.
Postoperative atrial fibrillation (POAF) is common after major surgeries and is associated with increased morbidity and mortality. POAF after liver transplantation (LT) has not been reported. This study was undertaken to investigate the incidence, impact, and risk factors of POAF in LT patients. After IRB approval, LT between January 2006 and August 2013 at our center were retrospectively reviewed. POAF that occurred within 30 days after LT was included. Patients with and without POAF were compared and independent risk factors were identified by logistic regression. Of 1387 adults LT patients, 102 (7.4%) developed POAF during the study period. POAF was associated with significantly increased mortality, graft failure, acute kidney injury and prolonged hospital stay. Independent risk factors included age, body weight, MELD score, presence of previous history of AF, the vasopressors use prior to LT and pulmonary artery diastolic pressure at the end of LT surgery (odds ratios 2.0-7.2, all p < 0.05). A risk index of POAF was developed and patients with the high-risk index had more than 60% chance of developing POAF. These findings may be used to stratify patients and to guide prophylaxis for POAF in the posttransplant period.
We report a rare case of primary osteosarcoma of the breast in a postmenopausal patient without any association to either trauma or an underlying tumor. Clinical, radiographic, and histologic illustrations as well as a review of the literature are presented.
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