Primary systemic amyloidosis presenting with advanced heart failure

Primary systemic amyloidosis (AL) is a rare, sporadic disease caused by deposition of immunoglobulin light chains in various tissues; symptoms vary based on which organs are infiltrated by the amyloid fibrils. Cardiac involvement occurs in up to 50% of patients with primary amyloidosis and is associated with a very poor prognosis. We report a case of a 57-year-old black man who presented with symptoms consistent with congestive heart failure. He was later found to have primary systemic amyloidosis, confirmed by abdominal fat pad biopsy.     

Very early risk stratification after thrombolytic therapy with a bedside myoglobin assay and the 12-lead electrocardiogram

BACKGROUND: Available clinical criteria to estimate prognosis in patients with evolving ST-segment elevation myocardial infarction do not consider the impact of reperfusion therapy and do not incorporate measurement of baseline levels of cardiac serum markers. We evaluated the combination of a baseline myoglobin assay and early (60- to 90-minute) ST resolution for risk stratification after ST-segment elevation myocardial infarction. METHODS: In a prospective substudy of the Intravenous nPA for Treatment of Infarcting Myocardium Early-II (InTIME-II) trial carried out in 2079 patients, a rapid qualitative assay for myoglobin was performed immediately before thrombolysis. Serial 12-lead electrocardiograms were performed at baseline and 60 to 90 minutes after thrombolysis. ST resolution was categorized as complete (>/=70%), partial (30% to <70%), or none (<30%). RESULTS: Mortality rate at 30 days was 3.3% in the 905 patients with a negative baseline myoglobin assay versus 8.9% in the 527 patients with a positive assay (P <.0001). Mortality rate was lowest (2.4%) among the 614 patients with complete ST resolution, intermediate (4.9%) among the 512 patients with partial ST resolution, and highest (8.1%) among the 540 patients with no ST resolution (P <.0001 for trend). In a logistic regression model incorporating other baseline predictors of 30-day mortality rate, both a positive myoglobin assay (relative risk 1.98, 95% confidence interval 1.00-3.90) and ST resolution <70% (relative risk 2.86, 95% confidence interval 1.22-6.69) were independently associated with increased mortality rate. At 30 days, mortality rate was 0.4% among patients with a negative myoglobin assay and complete ST resolution, 4.8% among patients with either a positive myoglobin assay or ST resolution <70%, and 9.6% among those with both a positive myoglobin ratio and ST resolution <70% (P <.001 for trend). CONCLUSIONS: Within 90 minutes after administering thrombolytic therapy for acute myocardial infarction, clinicians can determine the risk for death at the patient's bedside with a hand-held myoglobin assay and 2 serial 12-lead electrocardiograms. A strategy using these 2 simple, rapid, and inexpensive tests may facilitate triage after thrombolytic therapy.     

Performance of recombinant K39 antigen in the diagnosis of Brazilian visceral leishmaniasis

This study evaluated the performance of recombinant K39 (rK39) antigen in a immunochromatographic format (strip test) and a crude antigen enzyme-linked immunosorbent assay in the diagnosis of Brazilian visceral leishmaniasis (VL) in 128 consecutive patients with parasitologically proven infections (by microscopy and/or culture). For each patient, a medical history was obtained and a complete physical examination was performed. Controls included 10 healthy volunteers and 50 patients with other diseases: malaria (10), leprosy (9), Chagas' disease (10), tuberculosis (10), and cutaneous leishmaniasis (11). The sensitivities of the rK39 antigen strip test and the ELISA were 90% and 89%, respectively, while the specificities were 100% and 98%, respectively. Our study confirms the accuracy of the rK39 antigen strip test in the diagnosis of VL in a high prevalence population.     

Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18

OBJECTIVES: This study was designed to evaluate B-type natriuretic peptide (BNP) for risk assessment and clinical decision making over a range of cut points, alone and with cardiac troponin I (cTnI), in patients with non-ST-elevation acute coronary syndromes (ACS). BACKGROUND: B-type natriuretic peptide holds promise for risk stratification. Additional evidence regarding optimal decision limits, use in combination with troponin, and use in targeting therapy is needed before acceptance into clinical use for ACS. METHODS: We evaluated BNP at baseline in 1,676 patients with non-ST-elevation ACS randomized to early invasive versus conservative management. RESULTS: Patients with elevated BNP (>80 pg/ml; n = 320) were at higher risk of death at seven days (2.5% vs. 0.7%, p = 0.006) and six months (8.4% vs. 1.8%, p < 0.0001). The association between BNP and mortality at six months (adjusted odds ratio [OR] 3.3; 95% confidence interval [CI] 1.7 to 6.3) was independent of important clinical predictors, including cTnI and congestive heart failure (CHF). Patients with elevated BNP had a fivefold higher risk of developing new CHF by 30 days (5.9% vs. 1.0%, p < 0.0001). B-type natriuretic peptide added prognostic information to cTnI, discriminating patients at higher mortality risk among those with negative (OR 6.9; 95% CI 1.9 to 25.8) and positive (OR 4.1; 95% CI 1.9 to 9.0) baseline cTnI results. No difference was observed in the effect of invasive versus conservative management when stratified by baseline levels of BNP (p(interaction) > or = 0.6). CONCLUSIONS: Elevated BNP (>80 pg/ml) at presentation identifies patients with non-ST-elevation ACS who are at higher risk of death and CHF and adds incremental information to cTnI. Additional work is needed to identify therapies that may reduce the risk associated with increased BNP.     

Early outcome after sirolimus-eluting stent implantation in patients with acute coronary syndromes: insights from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry

OBJECTIVES: This study evaluated the early outcomes of patients with acute coronary syndromes (ACS) treated with sirolimus-eluting stents (SES). BACKGROUND: The safety of SES implantation in patients with a high risk for early thrombotic complications is currently unknown. METHODS: Sirolimus-eluting stents have been utilized as the device of choice for all percutaneous procedures in our institution, as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. After four months of enrollment, 198 patients with ACS had been treated exclusively with SES (64% of those treated in the period) and were compared with a control group composed of 301 consecutive patients treated with bare stents in the same time period immediately before this study. The incidence of major adverse cardiac events (MACE) during the first month was evaluated (death, nonfatal myocardial infarction [MI], or re-intervention). RESULTS: Compared with control patients, patients treated with SES had more primary angioplasty (95% vs. 77%; p < 0.01), more bifurcation stenting (13% vs. 5%; p < 0.01), less previous MI (28% vs. 45%; p < 0.01), and less glycoprotein IIb/IIIa inhibitor utilization (27% vs. 42%; p < 0.01). The 30-day MACE rate was similar between both groups (SES 6.1% vs. control patients 6.6%; p = 0.8), with most complications occurring during the first week. Stent thrombosis occurred in 0.5% of SES patients and in 1.7% of control patients (p = 0.4). In multivariate analysis, SES utilization did not influence the incidence of MACE (odds ratio 1.0 [95% confidence interval: 0.4 to 2.2]; p = 0.97). CONCLUSIONS: Sirolimus-eluting stent implantation for patients with ACS is safe, with early outcomes comparable with bare metal stents.     

Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas

The renin-angiotensin system plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. Besides angiotensin (Ang) II, other Ang peptides, such as Ang III [Ang-(2-8)], Ang IV [Ang-(3-8)], and Ang-(1-7) may also have important biological activities. Ang-(1-7) has become an angiotensin of interest in the past few years, because its cardiovascular and baroreflex actions counteract those of Ang II. Unique angiotensin-binding sites specific for this heptapeptide and studies with a selective Ang-(1-7) antagonist indicated the existence of a distinct Ang-(1-7) receptor. We demonstrate that genetic deletion of the G protein-coupled receptor encoded by the Mas protooncogene abolishes the binding of Ang-(1-7) to mouse kidneys. Accordingly, Mas-deficient mice completely lack the antidiuretic action of Ang-(1-7) after an acute water load. Ang-(1-7) binds to Mas-transfected cells and elicits arachidonic acid release. Furthermore, Mas-deficient aortas lose their Ang-(1-7)-induced relaxation response. Collectively, these findings identify Mas as a functional receptor for Ang-(1-7) and provide a clear molecular basis for the physiological actions of this biologically active peptide.     

A phylogenetic study of hepatitis B virus in chronically infected Brazilian patients of Western and Asian descent

Background  Hepatitis B virus (HBV) causes one of the most important chronic viral infections worldwide. HBV is classified into eight genotypes whose epidemiology varies geographically. In Brazil, genotypes A, D, and F are more frequent, while in East Asia, genotypes B and C predominate. Several studies showed that immigrants retain the HBV infection pattern of their ancestral country. Purpose  To identify HBV genotypes infecting chronic carriers in Brazilian families of Western and Asian descent by Hepatitis B surface antigen gene sequencing and analyze the route of viral transmission by phylogenetic analysis of viral sequences. Methods  Eighty-seven people chronically infected with HBV were separated into two groups: Western descent (27) and Asian descent (60). Surface and pre-core/core genes were amplified from serum HBV-DNA and sequences were subjected to phylogenetic analysis. Results  HBV genotype A was found in 74% of Western subjects, while genotype C was found in 94% of Asian patients. Thirty-eight percent of Western families were infected with HBV with similar pre-core/core sequences, while only 25% of Asian families showed similarity in these sequences. Conclusions  Phylogenetical analysis of pre-core/core HBV gene suggested intra-familial transmission of HBV in 38% of Western families and 25% of Asian families. Analysis of HBsAg gene sequences helped to define the HBV genotype but did not allow inferring route of transmission as its sequences showed a smaller phylogenetic signal than pre-core/core sequences. Chronic HBV carriers of Asian descent born in or living in Brazil were infected with the same HBV genotype predominant in their ancestral country.     

Relation of osteoprotegerin to coronary calcium and aortic plaque (from the Dallas Heart Study)

Circulating osteoprotegerin (OPG) has been shown to be elevated in patients with vascular disease. The role of OPG as a biomarker for atherosclerosis in a large, unselected population is not well known. Plasma OPG levels were measured in 3,386 subjects in the Dallas Heart Study, a multiethnic, population-based probability sample of adults aged 30 to 65 years. Coronary artery calcium (CAC) was measured by electron beam computed tomography. Aortic plaque was assessed by magnetic resonance imaging. Multivariable logistic regression was used to assess associations among OPG, cardiovascular risk factors, CAC, and aortic plaque. Age, female gender, black race, smoking, personal and family history of coronary artery disease (CAD), diabetes mellitus, hyperlipidemia, CAC, and aortic plaque were significantly associated with higher plasma OPG levels (p <0.01) in univariable analyses. The prevalence of CAC and aortic plaque increased across OPG quartiles (p <0.001 for each). An OPG level in the fourth quartile was independently associated with CAC (RR 1.39, 95% confidence interval 1.01 to 1.93) and aortic plaque (RR 1.42, 95% confidence interval 1.09 to 1.86) after adjustment for age, gender, smoking, diabetes, hyperlipidemia, and family history of premature CAD. In conclusion, plasma OPG is independently associated with CAC and aortic plaque in an unselected population, suggesting it may be a novel biomarker for atherosclerosis in humans.