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BACKGROUND: The prognostic value of Doppler myocardial imaging, including myocardial velocity imaging, strain, and strain rate imaging, in patients with primary (AL) amyloidosis is uncertain. The aim of this longitudinal study was to identify independent predictors of survival, comparing clinical data, hematologic and cardiac biomarkers, and standard echocardiographic and Doppler myocardial imaging measures in a cohort of patients with AL amyloidosis. METHODS: A total of 249 consecutive patients with AL amyloidosis were prospectively enrolled. The primary end point was all-cause mortality, and during a median follow-up period of 18 months, 75 patients (30%) died. Clinical and electrocardiographic data, biomarkers (brain natriuretic peptide and cardiac troponin T) and standard echocardiographic and longitudinal systolic and diastolic Doppler myocardial imaging measurements for 16 left ventricular segments were tested as potential independent predictors of survival. RESULTS: Age (hazard ratio [HR], 1.03; P = .03), New York Heart Association class III or IV (HR, 2.47; P = .01), the presence of pleural effusion (HR, 1.79; P = .08), brain natriuretic peptide level (HR, 1.29; P = .01), ejection time (HR, 0.99; P = .13), and peak longitudinal systolic strain of the basal anteroseptal segment (HR, 1.05; P = .02) were independent predictors in the final model. CONCLUSIONS: Multivariate survival analysis identified independent predictors of clinical outcome in patients with AL amyloidosis: New York Heart Association class III or IV, presence of pleural effusion, brain natriuretic peptide level > 493 pg/mL, ejection time < 273 ms, and peak longitudinal systolic basal anteroseptal strain less negative than or equal to -7.5% defined a high-risk group of patients.

Introduction: Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models.Methods: Data were pooled from six studies includi

Four isomeric homologs of lasalocid A have been isolated from cultures of Streptomyces lasaliensis. The homologs each arise by replacement of one of the four propionate derived methyls in lasalocid A by an ethyl group, which results in each homolog molecule containing four C-ethyls.

OBJECTIVE We hypothesized that the minor allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a general Mediterranean population. RESEARCH DESIGN AND METHODS We genotyped a random sample of the residents of Ventimiglia di Sicilia, Sicily, for rs5068. RESULTS Genotype frequencies of rs5068 are AA, 93.5%; AG, 6.4%; and GG, 0.1%. All subsequent analyses are AA versus AG+GG. After adjusting for age and sex, the minor G allele is associated with lower BMI (estimate [SE]: −1.7 kg/m2 [0.8], P = 0.04). In the AG+GG group, males with HDL cholesterol levels CONCLUSIONS The association between the minor allele of rs5068 and a favorable cardiometabolic phenotype that we previously reported in a U.S. population is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure, BMI, and prevalence of hypertension and metabolic syndrome. These findings may lead to a diagnostic strategy to assess cardiometabolic risk and lay the foundation for the future development of an ANP or ANP-like therapy for metabolic syndrome.

Background— Alterations at the level of the coronary circulation with aging may play an important role in the evolution of age-associated changes in left ventricular (LV) fibrosis and function. However these age-associated changes in the coronary vasculature remain poorly defined primarily due to the lack of high resolution imaging technologies. The current study was designed to utilize cardiac micro–computed tomography (micro-CT) technology as a novel imaging strategy, to define the 3-dimensional coronary circulation in the young and aged heart and its relationship to LV fibrosis and function. Methods and Results— Young (2 months old; n=10) and aged (20 months old; n=10) Fischer rats underwent cardiac micro-CT imaging as well as echocardiography, blood pressure, and fibrosis analysis. Importantly, when indexed to LV mass, which increased with age, the total and intramyocardial vessel volumes were lower, whereas the epicardial vessel volume, with and without indexing to LV mass, was significantly higher in the aged hearts compared with the young hearts. Moreover, the aged hearts had a significantly lower percentage of intramyocardial vessel volume and a significantly higher percentage of epicardial vessel volume, when normalized to the total vessel volume, compared with the young hearts. Further, the aged hearts had significant LV fibrosis and mild LV dysfunction compared with the young hearts. Conclusions— This micro-CT imaging study reports the reduction in normalized intramyocardial vessel volume within the aged heart, in association with increased epicardial vessel volume, in the setting of increased LV fibrosis, and mild LV dysfunction.

Aims To determine the role of assessing right ventricular (RV) function, using standard echocardiography and Doppler myocardial imaging (DMI), in the early diagnosis of cardiac amyloidosis and in the prediction of mortality. Methods and results Patients with primary systemic (AL) amyloidosis seen at our institution from 1 February 2004 through 31 October 2005 (N = 249) were categorized by left ventricular thickness and E′ velocity and compared with 38 age- and sex-matched controls. Standard echocardiographic and DMI examination were used to measure echocardiographic parameters of RV function: systolic tissue velocity, strain rate, and strain were determined for basal and middle RV free wall segments. Patients were followed up for the endpoint of mortality. RV tricuspid annular plane systolic excursion (TAPSE) and all DMI measurements were lower in patients with AL amyloidosis and normal echocardiography results (AL-normal-echo group) than controls. A bivariate model including strain of the basal segment of the RV free wall and TAPSE was the best for distinguishing AL-normal-echo patients from controls. Male sex [hazard ratio (HR), 2.2; P= 0.005], brain natriuretic peptide levels (HR 1.4; P= 0.003), troponin T levels (HR 1.6; P= 0.01), pleural effusion (HR 3.6; P< 0.001), E/A ratio (HR 1.3; P= 0.006), RV systolic pressure (HR 1.02; P= 0.01), and RV strain rate of the middle segment (HR 1.3; P= 0.02) were independent predictors of death. Conclusion DMI measures of the RV can identify early impairment of cardiac function or stratify risk of death in patients with AL amyloidosis. Further studies with longer follow-up are warranted to confirm these results.

Introduction: Atrial natriuretic peptide (ANP) possesses cardiorenal protective properties including natriuresis, aldosterone suppression and vasodilation. Importantly, ANP also exerts lipolytic effects in vitro and in vivo. Previous studies reported that the ANP genetic variant rs5068 is associated with increased plasma levels of ANP, lower blood pressure values, and reduced risk of hypertension. We recently reported that in a random sample of the general population from Olmsted County, MN the G allele of rs5068 was associated with increased levels of ANP, lower blood pressure and BMI, waist circumference, reduced prevalence of obesity and metabolic syndrome. To date, these associations have not been replicated. Hypothesis: The minor allele of rs5068 is associated with a favorable cardiometabolic phenotype in a randomly selected Mediterranean population. Methods: We genotyped a well characterized random sample of the residents of Ventimiglia di Sicilia, a small town in Sicily. Results: Genotype frequencies of rs5068 were AA: 93.5%, AG: 6.4%, and GG: 0.1%. All subsequent analyses are AA vs AG+GG. After adjusting for age and gender, the minor G allele was associated with lower systolic (120624 vs 126621 mmHg, p50.003) and diastolic (72610 vs 76610 mmHg, p50.03) blood pressure and lower BMI (26.764.9 vs 28.265.7 kg/m2, p50.04). Male subjects presenting HDL cholesterol plasma levels!40 mg/dL were less frequent in the AG+GG group (17% vs 27%,p50.05). Importantly, the G allele was significantly associated with a lower prevalence of metabolic syndrome (19% vs 32%, p50.02). Conclusions: The association between the minor allele of rs5068 and a favorable cardiometabolic phenotype, that we previously showed in a US population, is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure values, BMI, and prevalence of metabolic syndrome. These findings may lead to a diagnostic strategy to assess cardiometabolic risk and also lay the foundation for future development of an ANP or ANP-like therapy for metabolic syndrome.

ObjectivesThis study sought to investigate plasma levels of circulating cardiac natriuretic peptides, atrial natriuretic peptide (ANP) and B-type or brain natriuretic peptide (BNP), in the general community, focusing on their relative differences in worsening human hypertension.BackgroundAlthough ANP and BNP are well-characterized regulators of blood pressure in humans, little is known at the population level about their relationship with hypertension. The authors hypothesized that hypertension is associated with a lack of activation of these hormones or their molecular precursors.MethodsThe study cohort (N = 2,082, age >45 years) was derived from a random sample from Rochester, Minnesota, and each subject had a medical history, clinical examination, and assessment of different plasma forms of ANP and BNP. Patients were stratified by blood pressure. Multivariable linear regression was used to assess differences in natriuretic peptide levels in worsening hypertension.ResultsCompared to normotensive, BNP1–32 and N-terminal proBNP1–76 (NT-proBNP1–76) were significantly decreased in pre-hypertension (p < 0.05), with BNP1–32 significantly decreased in stage 1 as well (p < 0.05). Although proBNP1–108 remained unchanged, the processed form was significantly increased only in stage 2 hypertension (p < 0.05). ANP1–28 remained unchanged, while NT-ANP1–98 was reduced in pre-hypertension (p < 0.05).ConclusionsThe authors demonstrated the existence of an impaired production and/or release of proBNP1–108 along with a concomitant reduction of BNP1–32 and NT-proBNP1–76 in the early stages of hypertension, with a significant elevation only in stage 2 hypertension. Importantly, they simultaneously demonstrated a lack of compensatory ANP elevation in advanced hypertension.