Asymptomatic Cardiac Involvement Research Articles

Fragmented QRS complex, highly sensitive CRP, and fibrinogen in early detection of asymptomatic cardiac involvement in systemic lupus erythematosus

BackgroundPatients with systemic lupus erythematosus (SLE) have an increased risk of developing cardiovascular illnesses. Asymptomatic affection might exist, so early diagnosis can improve the outcome.AimThe purpose of this study was to determine the importance of highly sensitive C-reactive protein, fragmented QRS, and fibrinogen levels in identifying subclinical cardiac involvement in SLE patients, as well as how these variables relate to disease activity.ResultsRegarding hs-CRP and fibrinogen, there were significant differences between the SLE and control group, with a higher frequency of fQRS in the lupus group. The lupus group was divided into 2 subgroups: 44 patients with fragmented QRS in ECG (83%) and 9 patients with normal QRS (17%) with a higher mean value of hs-CRP and fibrinogen level (58.76 ± 70.15, 18.54 ± 26.79) and low HDL (53.37 ± 10.37) in those with fQRS ( +). The sensitivity and specificity of hs-CRP at a cut of level (3.5 mg/L) for fQRS in SLE patients were 75.5%, and 71.7%, respectively. Regression analysis showed hs-CRP and were significant predictors for fQRS changes in SLE patients.ConclusionsA more thorough evaluation of SLE patients with fQRS complexes with hs-CRP and fibrinogen is important with close follow-up for the detection of subclinical cardiac involvement in SLE. Also, SLE activity is linked to fQRS and fibrinogen. Therefore, we advise using them for additional medical care for lupus.

Prothrombotic state, endothelial injury, and echocardiographic changes in non-active sarcoidosis patients.

Sarcoidosis is a multisystem inflammatory granulomatous disease of unknown cause that most commonly affects lungs and lymph nodes, with frequent yet asymptomatic cardiac involvement. The epidemiologically associated cardiovascular risk suggests an underlying prothrombotic state and endothelial dysfunction, currently understudied in the available literature. Therefore, we aimed to investigate prothrombotic plasma properties together with selected echocardiographic and laboratory biomarkers of cardiovascular injury in that disease. N = 53 patients with pulmonary sarcoidosis in clinical remission and N = 66 matched controls were assessed for inflammatory and endothelial injury biomarkers, plasma thrombin generation profile, and echocardiographic and lung function parameters. Sarcoidosis cases had impaired systolic and diastolic left ventricular function, higher concentrations of inflammatory markers, D-dimer and factor VIII activity compared to the controls. The coexistence of extrapulmonary disease was associated with elevated circulating vascular cell adhesion molecule 1, while cases with hypercalcemia had higher thrombomodulin concentration. Sarcoidosis was characterized by the unfavorably altered thrombin generation profile, reflected by the 16% higher endogenous thrombin potential (ETP), 24% increased peak thrombin concentration, and 12% shorter time to thrombin peak in comparison to the control group. ETP was higher in cases with proxies of pulmonary restriction, extrapulmonary-extracutaneous manifestation, and need for corticosteroids use. Despite the clinical remission, sarcoidosis is related to prothrombotic plasma properties and signs of endothelial injury, likely contributing to the higher risk of cardiovascular events. In addition, subclinical cardiac involvement may play an additional role, although further clinical and experimental studies are needed to verify these findings.

Cardiotoxicity of perioperative chemotherapy for neublastoma in pediatric visceral surgery

Neuroblastoma is a cancer of the sympathetic nervous system, which accounts for 7% of all childhood cancers and 15% of childhood cancer deaths. During the diagnosis and treatment of these pediatric cancers, children have a high-risk of developing cardiotoxicity due to chemotherapy and perioperative decompensation of this heart disease. The management of side effects mainly involves screening for risk situations based on clinical examination, ECG and echocardiography, mainly preoperatively. The main objective of this study was the cardiac assessment of patients scheduled for neuroblastoma excisional surgery who are on neoadjuvant chemotherapy. Our sample was 20 patients. Average age was 3 years (13 months–6 years) with male predominance, the sex ratio M/F is 1.4. The abdominal seat represented 70% (14 cases) of all locations, the thoracic seat represented 20% (4 cases) of the locations, the pelvic seat represented 10% of the locations. Sixty percent of neuroblastomas were metastatic at the time of diagnosis. Spinal cord infiltration accounted for 60% of all metastatic cases. All of our patients were receiving an anthracycline as part of their chemotherapy regimen, which caused heart damage. The pre-anesthetic clinical examination assessed dyspnea according to the NYHA (New York Heart Association) class. NYHA class I dyspnea was found in 15 patients (75%) of patients. NYHA class II dyspnea was found in 4 patients (20%) of the patients. NYHA class III dyspnea was found in one patient (5%) of patients with pulmonary metastases. NYHA stage IV dyspnea has not been found in any patient. In our study, 40% of cases or 8 patients retained their cardiac function under anthracyclines, 50% or 10 patients developed a moderate to slight decrease in cardiac function. Two patients or 10% of cases developed severe cardiotoxicity with one case of symptomatic cardiac involvement and one case of asymptomatic cardiac involvement. This required a discontinuation of treatment and hospitalization in intensive care in a picture of cardiomyopathy. The two patients with impaired systolic function were put on an Angiotensin-converting enzyme inhibitor. We observed regression of dyspnea and signs of heart disease with improvement in left ventricular ejection fraction. There have been no deaths from heart failure. We changed the chemotherapy protocol with stopping the anthracyclines. We advocated careful ultrasound monitoring for patients with mild to moderate cardiotoxicity. The diagnosis of cardiovascular complications associated with chemotherapy must be early. Cardiopulmonary complications are the third leading cause of death after primary cancer recurrence and the onset of a second cancer.

Clinical Outcomes of Asymptomatic Cardiac Involvement in Systemic Sclerosis Patients After a 2-Year Follow-Up (Extended Study)

Asymptomatic cardiac involvement in systemic sclerosis (SSc) has been reported. Long-term follow-up might elucidate the clinical implications of these abnormalities. The aim was to identify the clinical outcomes of asymptomatic cardiac involvement in SSc patients after 2 years of follow-up. A cohort study was done at Khon Kaen University, Thailand, on adult patients with SSc who completed the preliminary study. Repeated investigations included electrocardiography, chest radiography, echocardiography, and blood tests for creatine kinase-MB, high sensitivity cardiac troponin-T, and N-terminal prohormone of brain natriuretic peptide. Seventy-four of the 103 patients from the previous study were enrolled. The mean duration of follow-up was 3.1±0.9 years. Five patients developed symptomatic cardiac involvement-all of whom had pulmonary arterial hypertension (PAH). The incidence of symptomatic cardiac involvement for the combined 315 person-years was 1.6 per 100-person-years (95%CI 0.7-3.4). Fourteen patients died resulting in a mortality incidence of 4.4 per 100-person-years (95%CI 4.3-5.4). Persistent cardiac involvement was found in 35 patients for an incidence of 11.1 per 100-person-years (95%CI 8.0-15.5). Two of the patients who had persistent elevated cardiac enzyme developed PAH at a respective 3.7 and 39.4 months after the initial evaluation. None of the clinical parameters were predictive of symptomatic and persistent cardiac involvement. Only male sex was associated with mortality (hazard ratio 3.70; 95%CI 1.22-11.11). Cardiac involvement in SSc can progress slowly or even be reversed. Based on a previous test, the incidence of symptomatic cardiac involvement after 2 years was low despite its being a persistent involvement. If symptomatic cardiac involvement develops, PAH is the most prevalent symptom.

Detection of cardiac amyloidosis by PET/CT imaging using 124I-p5+14 peptide

Abstract Introduction Systemic amyloidosis is characterized by the deposition of protein fibrils in abdominothoracic organs, notably the heart, leading to organ dysfunction and significant morbidity. Patients who present with light chain (AL) amyloid-associated cardiomyopathy have a poor prognosis and median survival of only ∼ 9 mos. Cardiac amyloidosis is also present in many of the other forms of the disease and may be ever present in patients with transthyretin-associated amyloidosis (ATTR). Currently, no radiotracers are approved for the quantitative imaging of cardiac amyloid load. To address these needs, we have developed a synthetic amyloid-reactive peptide radiotracer, 124I-p5+14, suitable for PET/CT imaging. The peptide binds the three major forms of amyloid (AL, ATTR and ALECT2), as well as other, less common, types through multivalent electrostatic interactions with amyloid-associated glycosaminoglycans and fibrils. Herein we report safety, dosimetry, and efficacy data on the first 22 patients from the ongoing Phase 1, first-in-human trial of 124I-p5+14 in patients with systemic amyloidosis (NCT 03678259). Methods Patients >18 years of age with a confirmed diagnosis of systemic amyloidosis and not requiring heparin therapy are eligible. Subjects received <2 mg of 124I-p5+14 (<2 mCi) administered as a single IV bolus. PET/CT images for the initial cohort (n=3) were acquired from 25 min to 48h post injection. The second cohort of patients were imaged at ∼5 h and 24 h post injection. Image data were acquired using a Biograph 16 PET/CT scanner with a low dose CT. Uptake of radiotracer in the left ventricular wall was performed by automated image segmentation and standard uptake value ratios (SUVR) were calculated using blood pool as the reference tissue. Results To date, 22 patients (13 AL, 5 ATTR, and 4 other) patients have been evaluated. The gender-averaged mean whole body effective dose was 0.24 mSv/MBq. Cardiac uptake of the radiotracer was visually detected by a reader blinded to the patients' organ involvement in 85% and 100% of patients with AL and ATTR respectively, including patients with asymptomatic cardiac involvement - no cardiac symptoms or elevated cardiac biomarkers. The mean myocardium SUVR for visually positive AL and ATTR patients were 2.2±0.6 and 2.6±0.4. For visually negative AL patients the SUVRs were 1.0 and 0.9. In addition to cardiac amyloid, 124I-p5+14 uptake was observed in the nerves, ligaments, liver, spleen, adrenal glands, kidneys, pancreas, pituitary, and lung, with overall abdominothoracic organ-specific sensitivity of >90% based on clinical presentation. Sensitivity in the heart was 100%. Conclusions PET/CT imaging of 124I-p5+14 provides excellent visualization of AL and ATTR cardiac amyloidosis which can be readily quantified as a means of monitoring response to therapy or disease progression. The 124I-p5+14 radiotracer was also capable of detecting amyloid in other abdominothoracic organs. AL and ATTR cardiac amyloidosis Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart Lung and Blood Institute, National Institutes of Health; ACTP Gift Fund at the UTGSM

Cardiac Sarcoidosis.

Approximately 5% of patients with sarcoidosis will have clinically manifest cardiac involvement presenting with one or more of ventricular arrhythmias, conduction abnormalities, and heart failure. It is estimated that another 20 to 25% of pulmonary/systemic sarcoidosis patients have asymptomatic cardiac involvement (clinically silent disease). Cardiac presentations can be the first (and/or an unrecognized) manifestation of sarcoidosis in a variety of circumstances. Immunosuppression therapy (usually with corticosteroids) has been suggested for the treatment of clinically manifest cardiac sarcoidosis (CS) despite minimal data supporting it. Positron emission tomography imaging is often used to detect active disease and guide immunosuppression. Patients with clinically manifest disease often need device therapy, typically with implantable cardioverter defibrillators (ICDs). The extent of left ventricular dysfunction seems to be the most important predictor of prognosis among patients with clinically manifest CS. In the current era of earlier diagnosis, modern heart failure treatment, and use of ICD therapy, the prognosis from CS is much improved. In a recent Finnish nationwide study, 10-year cardiac survival was 92.5% in 102 patients.

A low perfusion-metabolic mismatch in 99m Tl and 123 I-BMIPP scintigraphy predicts poor prognosis in systemic sclerosis patients with asymptomatic cardiac involvement.

This study investigated the prognostic factors of cardiac death or cardiac failure using cardiac scintigraphy, echocardiography (UCG), and magnetic resonance imaging (MRI) in asymptomatic systemic sclerosis (SSc) patients. We retrospectively evaluated SSc patients who had undergone cardiac scintigraphy using 99m thallium (99m Tl) and 123 I-β-methyl-P-iodophenyl-pentadecanoic acid (123 I-BMIPP), UCG, and cardiac MRI. We calculated the mismatch score in scintigraphy by subtracting the uptake of 123 I-BMIPP from that of 99m Tl. Patients were divided into two groups according to whether they survived with no cardiac failure or subsequently proceeded to cardiac failure or death during the study period. We identified prognostic factors by analyzing 99m Tl and 123 I-BMIPP uptake, mismatch scores, UCG findings, and cardiac delayed enhancement on MRI. We also evaluated pathological evidence of myocardial fibrosis. Of 33 SSc cases, 11 proceeded to cardiac failure or death. There was no significant difference in UCG or MRI findings between the two groups. Low mismatch score in cardiac scintigraphy was the only predictive factor of cardiac failure or death by multivariate analysis (odds ratio, 6.48; 95% confidence interval, 1.22-423.2; P=0.01). When patients were grouped according to high or low mismatch scores based on a cut-off using receiver operating characteristics curve analysis, the cumulative incidence of cardiac failure or death was higher in the low mismatch group than in the high mismatch group (P=0.02). The percentage of fibrosis was significantly higher in deceased cases compared to surviving cases. Low mismatch score in cardiac scintigraphy was associated with cardiac death or cardiac failure in SSc patients.

Early detection of left ventricular involvement in patients with Duchenne’s and Becker’s muscular dystrophy

Background Patients with Duchenne muscular dystrophy (DMD) and Becker’s muscular dystrophy (BMD) may have asymptomatic cardiac involvement for years before the development of dilated cardiomyopathy and even showed normal conventional echocardiographic parameters. We evaluated those patients with more recent echo modalities for early detection of subtle cardiac changes. Patients and methods Thirty patients [13 with BMD as group 1 (G1) and 17 with DMD as group 2 (G2)] compared with 30 age-matched and sex-matched healthy participants as group 3 (G3). All cases were subjected to history taking, clinical examination, ECG, conventional two-dimensional (2D) echocardiography, tissue Doppler imaging, 2D-speckle tracking echocardiography, and 4D echocardiography for measurement of left ventricular (LV) dimensions, systolic and diastolic function with focus on strain imaging modality. Results Nine patients of G2 and three patients in G1 had LV systolic dysfunction despite normal 2D-LV ejection fraction. Ten patients in G2 and five patients in G1 had LV diastolic dysfunction measured by LV early diastolic wave velocity over mitral valve measured by conventional Doppler/early diastolic mitral annular velocity by tissue Doppler imaging (E/Ea). Tissue Doppler myocardial performance index was significantly higher in both G1 and G2. 2D-LV septal strain, lateral strain, anteroseptal, 2D-global longitudinal strain (GLS), and 4D-GLS strains were significantly lower in G1 and G2. Apical, mid, and basal posterior LV strain were significantly lower in G2 compared with G1. 2D-GLS was lower in G2 compared with G1. Both LV global radial strain and global circumferential strain were significantly lower in G1 and G2. Mid and basal septal strain and basal posterior strain were significantly lower in G2 compared with G1. The mid and basal posterior strains were significantly lower in G2 compared with G1. Conclusion 2D-speckle tracking and 4D echocardiographic study of global and regional strain besides creatinine phosphokinase serum levels may add benefit in early detection of subtle LV dysfunction in patients with DMD and BMD.

Cardiac Involvement in Sarcoidosis Deaths in Wayne County, Michigan: A 20-Year Retrospective Study.

Sarcoidosis is a disease of unknown etiology characterized by the formation of noncaseating, nonnecrotizing granulomas in various organ systems. Reviews of 84 cases of natural death with sarcoidosis between the years 1996 and 2017 autopsied at Wayne County. The median age of decedents was 44 years (29 - 59 years of age). Blacks comprised 95% of the cohort, and 52% were female. Sarcoidosis or direct sequelae were the cause of death in 79% of cases. Twenty-nine percent of patients had a documented history of sarcoidosis and 70% of patients had evidence of systemic sarcoidosis. The most common sites of involvement were lungs or hilar lymph nodes (92%), heart (45%), liver (39%), and spleen (30%). Decedents with cardiac involvement were more likely to have no documented history of sarcoidosis (87% vs. 59%, p=0.004), more likely to have died of a sarcoidosis-related cause (97% vs. 65%, p<0.001), and died at a younger mean age (41 years vs. 46 years, p=0.001). In addition, individuals with cardiac involvement commonly had concurrent multiorgan involvement including lungs (90%), lymph nodes (38%), liver (40%), spleen (32%), and kidneys (7%). Cardiac sarcoidosis is a uniquely poor prognostic factor and carries an increased risk of sudden death as shown by a disproportionate representation among medical examiner cases of sarcoidosis. Our findings suggest that approximately 40% may have asymptomatic cardiac involvement. The distribution of sarcoidosis within our cohort suggests that there is potentially a large undiagnosed and/or underdiagnosed demographic within large urban centers, such as Detroit, Michigan.

An anaplastic cardiac large cell lymphoma: A case report and analysis of cardiac involvement in newly diagnosed non-Hodgkin’s lymphoma from the Czech Lymphoma Study Group (CLSG) database

We report a rare case of anaplastic large cell ALK+ lymphoma (ALCL) with initial asymptomatic cardiac involvement. A 59-year-old male with infiltration of the right ventricular wall underwent standard combined chemotherapy (CHOP) and achieved remission without significant cardiac impairment. Additionally, we report the actual incidence of cardiac lymphoma in newly diagnosed non-Hodgkin Lymphomas (NHLs). In total, 16 patients with cardiac lymphoma were found (0.1% NHLs) in the Czech Lymphoma Study Group database. DLBCL was the most frequent histology subtype (50%), and ALCL was identified in 12.5% of cases. At initial diagnosis, the median age was 55.5 (range 21-74) years and 59% were men. None of the 16 patients with cardiac involvement had isolated heart lymphoma. The response to first-line therapy was 79% in 14/16 evaluable patients. The median progression-free survival and overall survival were nearly the same -approximately 3.5 years (range; 0.05-16.7ys), while the median follow up was 4 years.

Cardiac manifestations of sarcoidosis: diagnosis and management.

Approximately 5% of patients with sarcoidosis will have clinically manifest cardiac involvement presenting with one or more of ventricular arrhythmias, conduction abnormalities, and heart failure. Cardiac presentations can be the first (and/or an unrecognized) manifestation of sarcoidosis in a variety of circumstances. Cardiac symptoms are usually dominant over extra-cardiac as most patients with clinically manifest disease have minimal extra-cardiac disease and up to two-thirds have isolated cardiac sarcoidosis (CS). It is estimated that another 20-25% of pulmonary/systemic sarcoidosis patients have asymptomatic cardiac involvement (clinically silent disease). The extent of left ventricular dysfunction seems to be the most important predictor of prognosis among patients with clinically manifest CS. In addition, the extent of myocardial late gadolinium enhancement is emerging as an important prognostic factor. The literature shows some controversy regarding outcomes for patients with clinically silent CS and larger studies are needed. Immunosuppression therapy (usually with corticosteroids) has been suggested for the treatment of clinically manifest CS despite minimal data supporting it. Fluorodeoxyglucose Positron Emission Tomography imaging is often used to detect active disease and guide immunosuppression. Patients with clinically manifest disease often need device therapy, typically with implantable cardioverter defibrillators.

The heart and pulmonary arterial hypertension in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed. Both diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subgroups are at risk for cardiac involvement and SSc-PAH. Cardiac involvement can be divided in pericardial involvement, myocardial involvement and rhythm disturbances and mostly occurs asymptomatically. However, when symptomatic, it is associated with a poor prognosis. Screening for asymptomatic cardiac involvement should be considered in SSc in order to initiate treatment in an early stage. However, there are no randomized controlled trials on treatment options for cardiac involvement in SSc. SSc-PAH is a devastating complication of SSc, which can develop early in DcSSc and LcSSc. Screening for PAH should be performed since screening leads to earlier diagnosis and earlier treatment is associated with a better prognosis. Today, screening is performed by clinical judgement and echocardiography. Recently the DETECT algorithm, a 2-step screening algorithm is proposed in a SSc-subgroup at increased risk for PAH, but further validation is needed. Despite current treatment options with prostacyclins, endothelin-1 receptor antagonists and phosphodiesterase type-5 inhibitors, mortality remains high. Several promising new treatment options for PAH are evaluated in phase II and III clinical trials.

Study of cardiovascular manifestations in patients of HIV- its correlation with CD4 count and the ART regimen prescribed

Background: In patients of HIV, there is correlation of CD4 count with severity of cardiac involvement. Some HAART regimens are associated with increased risk for cardiovascular events. This study was undertaken to detect occurrence of symptomatic or asymptomatic cardiac involvement in HIV/AIDS cases. Correlation with CD4+Tcell count and the ART regimen prescribed was also studied. Methods: This single point cross sectional case control study of 103 patients with HIV infection on HAART therapy was studied from April 2014 to August 2015. The study population was investigated for routine blood tests, X-Ray chest PA view, ECG, CD4 count and 2D transthoracic echocardiography. Results: The cases comprised of 43 females (41.75%) and 60 males (62.0%). Mean CD4 count was 205.48±150.06/µL and on X-ray chest PA view cardiomegaly was found in 40.78% of cases. The ECG findings were sinus tachycardia (19.42%), left axis deviation (5.82%), low voltage complexes (16.5%), right axis deviation (16.5%) intraventricular conduction delay (5.82%) and ST-T changes (8.7%) The echocardiographic findings were left ventricular diastolic dysfunction (60.24%), pericardial effusion (15.53%), dilated cardiomyopathy (23.03%), pulmonary artery hypertension (17.47%) and valvular lesions (33%). Conclusions: Declining CD4 count was associated with increased cardiac manifestations but no statistically significant difference was found in both the (TLE and ZLN) subgroups.

Asymptomatic cardiac involvement in Thai systemic sclerosis: prevalence and clinical correlations with non-cardiac manifestations (preliminary report).

To determine the prevalence of asymptomatic cardiac involvement and its correlation with non-cardiac manifestation in Thai SSc patients. A cross-sectional study was carried out between January 2012 and June 2013 at Srinagarind Hospital, Khon Kaen University, Thailand, on adult SSc patients without signs or symptoms suggestive of cardiac involvement. We excluded those with overlap syndrome, having serum creatinine >123.8 µmol/l, history of cardiac diseases, any atherosclerosis risk factors and receiving angiotensin-converting enzyme inhibitors. Non-invasive tests related to cardiac involvement were performed, including: echocardiography, ECG, chest X-ray, inflammatory biomarkers, cardiac enzymes and N-terminal prohormone of brain natriuretic peptide. A total of 103 SSc patients were enrolled, 61.2% of whom were in the subset. Of these, 63 patients had at least one test abnormality (prevalence 61.2%; 95% CI 51.6, 70.7). The two leading cardiac abnormalities were diastolic dysfunction (44.7%) and elevation of cardiac enzymes (36.9%). The only predictor for cardiac involvement per multivariate analysis was the dcSSc subtype with a higher modified Rodnan skin score, and shorter disease duration (odds ratio = 3.37; 95% CI 1.07, 10.65). Compared with the limited subtype, dcSSc was also significantly associated with elevated cardiac enzyme and prolonged distance between a Q wave and T wave in an ECG (QT interval). Asymptomatic cardiac involvement in Thai SSc was not uncommon, and the most common finding was diastolic dysfunction. Elevated cardiac enzymes were found in one-third of the patients, which correlated with the dcSSc subtype with a higher modified Rodnan skin score and shorter disease duration, suggestive of early myocardial microcirculation disruption. Long-term follow-up was performed to elucidate the clinical implication of these abnormalities.

Myocardial stress perfusion-fibrosis imaging pattern in sarcoidosis, assessed by cardiovascular magnetic resonance imaging

Sarcoidosis (SRC) is characterized by granulomas in various organs,including the heart [1]. We hypothesized that cardiovascular magneticresonance (CMR) may diagnose silent heart lesions in SRC.Forty five consecutive, asymptomatic patients with SRC, (14 men,45 ± 3 years) normal echocardiogram and 24-hour ECG, underwentCMR imaging, using a 1.5 T. Steady-state, free precession cines wereacquired for function evaluation and STIR T2-W for edema imaging.For SRC with T2 ratiob 2(GroupA)andT2ratioN 2(GroupB),astress perfusion-fibrosis (Fig. 1) and a myocarditis protocol (Fig. 2)were applied, respectively and were compared to 45 age–sexmatched controls.CMRwasperformedin43/45patients(2wereexcludedduetotech-nical reasons). In 34/43 SRC with T2 ratio b 2 (Group A), a stressperfusion-fibrosis CMR revealed a significant reduction in myocardialperfusion reserve index (MPRI), compared to34age–sex matched con-trols(0.95±0.3vs3.5±0.8,p b 0.001).Althoughclearevidenceoflategadolinium enhancement was not identified, the quantitative analysisrevealed diffuse fibrosis in all patients with an extent of 4.5 ± 3.4% LV(range2–15).AvailableCMRafter1yearin18/34patients,documentedLVEF b 50% in 3 patients. Notably, in 6/9 SRC patients with T2 ratio N 2(GroupB),themyocarditis protocol was positive and steroid treatmentwaspromptly given.Sixmonthslater, their CMRwasnormal. Nocorre-lation between CMR, SRC duration and/or other organs involvementwas identified. Detailed CMR parameters of SRC patients are presentedin Table 1.Cardiac involvement, according to pathology, may occur in 20–30%of SRC of patients [1],andhasbeenassociatedwithpoorprognosis[2].Despite these findings, only 5% of SRC have clinical manifestations ofcardiac disease, and only 40–50% of those with cardiac SRC at autopsyhave the correct diagnosis during lifetime [2].CMRhasbeenrecentlyconsideredasthebestnoninvasivetooltoas-sess the presence of fibro-granulomatous tissue in the myocardium inSRC [3]. Smedema et al. reported that the prognosis of asymptomaticSRC patients with cardiac involvement is better compared to SRC pa-tients with symptomatic cardiac SRC [4]. Therefore, a positive CMR inasymptomatic SRC offers the advantage of early treatment and betterprognosis [4]. Greulich et al. found that among SRC with nonspecificsymptoms, myocardial LGE was the best independent predictor of po-tentiallylethalevents[5].IncontrasttoLGEthatdetectstheareaalreadyreplaced by the fibro-granulomatous tissue, sarcoid infiltrates may alsobe visible as increased intramyocardial signal on T2-weighted images,due to edema, associated with granulomatous lesions.In ourasymptomaticSRC, acute myocardialinflammationwasiden-tified by CMR in 14%, characterized by both edema and positive LGE.This was in agreement with previous studies [6] and motivated earlysteroidtreatment;noneofthesteroids-treatedpatientsdevelopedclin-ically overt cardiac SRC in the next 6 months; furthermore, they nor-malized their CMR. Our findings are in agreement with recent data,showing that the prognosis of asymptomatic cardiac involvement inpulmonary SRC remains good [6].Microvascular disease in SRC has been identified in different organs[7]. Reversible myocardial perfusion defects have been already

Elevated Cyclin D1 (CCND1) Expression in the Plasma Cells of Patients with Systemic AL Amyloidosis at Diagnosis Is Associated with Higher Brain Natriuretic Peptide (BNP) Levels, Increased Plasma Cells and Significantly Poorer Survival.

Abstract 2815Poster Board II-791 Background:The clonal plasma cells in AL can be considered malignant because they contain cytogenetic abnormalities, including t(11;14) in 40% to 50% of cases (Blood 2001;98:2266; 2008;111:4700; Haematologica 2009;94:380). By gene expression profiling (GEP) they are also reported to overexpress CCND1 (Blood 2005;105:794). To assess the frequency and significance of differences in CCND1 expression in plasma cells from AL patients at diagnosis, we evaluated the differences in CCND1 expression in CD138+ plasma cells from newly diagnosed patients. We then correlated these differences with features of both the deposition and clonal plasma cell diseases, and with treatments, outcomes and overall survival. Methods:Newly diagnosed AL patients were evaluated and CD138+ cells selected and used for GEP with Affymetrix U133 PLUS2.0 arrays (Affymetrix; Santa Clara, CA) or qRT-PCR as previously described (JNCCN 2007;5:179; Blood 2008;111:549). qRT-PCR was performed using TaqMAN Gene Expression Assays with CCND1 (Hs00277039_m1) and RPLP0 (Hs99999902_m1) primers and probes (Applied Biosystems; Foster City, CA) and 2 myeloma cell lines as positive and negative controls (KMS-12BM, RPMI 8226) on an Mx 3000P platform and related software (Stratagene; La Jolla, CA). The comparative Ct method was used and the amount of target was normalized to the control (2-ΔΔCt) assuming an efficiency of 2. Statistical analyses were performed with GraphPad PRISM (GraphPad; La Jolla, CA). Results:CD138+ cells from 58 newly diagnosed AL patients were evaluated. With GEP (n=16), CCND1 median loge-transformed quantitative expression levels were 11.08 (range, 9.6-11.55) in five versus 4.163 (3.875-5.447) in eleven patients (P < 0.01). With qRT-PCR (n=42), relative CCND1 expression levels were 4.21 (1.76-17.24) in twenty versus 0.014 (0-0.99) in twenty-two patients (P < 0.0001). Overall, 43% (25/58) of patients were CCND1+ and did not differ from CCND1- patients with respect to organ involvement, troponin I, urine total protein, creatinine or alkaline phosphatase levels. The median BNP of CCND1+ patients was 252pg/ml (range 20-1880), significantly higher than that of CCND1- patients (109pg/ml (5-4210), P < 0.05). CCND1+ patients tended to have more plasma cells (13% versus 8%, P = 0.06), higher serum free light chain levels (23.3 versus 14mg/dl, P = 0.12) and more kappa clones (6/25 versus 2/33, P = 0.06), and had fewer intact immunoglobulin M-proteins (4/25 versus 22/33, P < 0.01). There were no differences in frequencies of treatment with stem cell transplant or oral melphalan/dexamethasone or in the rates of complete hematologic responses. CCND1+ patients survived a median of only 27 months compared to 60 months for CCND1- patients (P = 0.02) and had a risk of death of 2.86 (CI 1.18-6.94). Conclusions:Significant differences in CCND1 expression in the plasma cells of AL patients at diagnosis can be appreciated by GEP and qRT-PCR and clearly define two groups, CCND1+ and CCND1-, that differ in baseline BNP levels and features of the clonal plasma cell disease. Despite similar treatments and initial responses, CCND1+ patients have poorer overall survival, possibly due to asymptomatic cardiac involvement at diagnosis and low-level persistence of clonal plasma cells despite treatment, hypotheses that merit prospective evaluation. Disclosures:Comenzo:Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Asymptomatic Cardiac Involvement in Children with Systemic Lupus Erythematosus

Asymptomatic Cardiac Involvement in Children with Systemic Lupus Erythematosus

Cardiac Involvement in Patients With Pulmonary Sarcoidosis Assessed at Two University Medical Centers in the Netherlands

We aimed to determine cardiac involvement in patients with pulmonary sarcoidosis (PS) followed up at two university medical centers in the Netherlands. We reviewed the findings in consecutive patients assessed by our departments during 1998 to 2004, and classified them as patients who had presented with symptoms of cardiac sarcoidosis (CS) [group A], and those who had been screened for this condition (group B). Two university medical centers in the Netherlands. One hundred one patients (69 men [mean age, 47.6 years] and 32 women [mean age, 47.3 years]) with biopsy-proven PS. Twelve-lead ECG (n = 101), ambulatory ECG (n = 74), echocardiography (n = 80), (201)Tl single-photon emission CT (n = 61), cardiac MRI (n = 87), coronary angiography to exclude coronary artery disease (n = 17), and endomyocardial biopsy (n = 9). ECG, structural, and functional cardiac abnormalities according to the modified guidelines of the Japanese Ministry of Health and Welfare (1993). Sixteen of 19 patients in group A and 3 of 82 patients in group B received a diagnosis of CS. During a mean follow-up of 1.7 years (range, 3 months to 4 years), four patients in group A died (20%) and nine patients received a pacemaker and/or an implantable cardioverter-defibrillator (47%), while the patients in group B had an uncomplicated course. Once symptomatic CS develops in PS patients, the prognosis becomes very grim. In contrast, the prognosis in asymptomatic cardiac involvement in PS patients is good. Considering the poor prognosis of symptomatic CS, pulmonologists should consider regular screening of their PS patients for cardiac involvement with straightforward detection methods.

360 Immune-related asymptomatic cardiac involvement in human immunodeficiency virus infection: An echocardiographic study

360 Immune-related asymptomatic cardiac involvement in human immunodeficiency virus infection: An echocardiographic study

Combined atrial septal aneurysm and mitral valve prolapse: Detection by two-dimensional echocardiography

vation consistent with the high incidence of asymptomatic cardiac involvement in familial amyloid. 3 Because cardiac symptoms did not develop in our patients during follow-up, we believe that the significance of these findings lies not in any short-term prognostic value of cardiac pyrophosphate scintigraphy, but rather as an aid to diagnosis in the patient with an obscure familial polyneuropathy and abnormal echocardiogram. A positive scintigram in such a patient indicates the need for further diagnostic studies with appropriate tissue staining, such as abdominal fat aspiration or peripheral nerve biopsy. 5