Citations

Podocyturia, the shedding of live podocytes, is present at delivery in women with preeclampsia. The aim of this study was to test whether podocyturia is present earlier in pregnancy and predicts for preeclampsia. We also aimed to compare test characteristics of podocyturia with those of angiogenic factors previously implicated in the pathogenesis of this disorder. We prospectively enrolled 315 women who provided blood and urine samples at the end of the second trimesters of their pregnancies (median, 27 gestational weeks) and within 24 hours of their deliveries (median, 39.5 gestational weeks). Blood samples were analyzed for angiogenic markers, including placental growth factor, the soluble receptor fms-like tyrosine kinase receptor-1 for vascular endothelial growth factor, and endoglin. The urine sediments were analyzed for podocytes, identified by staining for podocin after culturing the urinary sediments for 24 hours. This analysis included all women who developed preeclampsia (n=15), gestational hypertension (n=15), and a subsample of women who remained normotensive throughout pregnancy (n=44), matched for maternal age and number of previous pregnancies to those who developed preeclampsia. At the second trimester collection, all women who developed preeclampsia had podocyturia, compared with none of those who remained normotensive or were diagnosed with gestational hypertension. Podocyturia in the second trimester had a significantly greater sensitivity and specificity for the subsequent diagnosis of preeclampsia than any single angiogenic marker or a combination thereof. Screening for podocyturia at the end of the second trimester may allow for accurate identification of pregnant women at risk for preeclampsia.

Background— Implantable cardioverter-defibrillator system efficacy is tested at implant by induction of ventricular fibrillation (VF). Defibrillation safety margin can be assessed without VF induction using upper limit of vulnerability methods, but these methods have required manual determination of T-wave timing. Methods and Results— To test the feasibility of an inductionless system of implant testing, a multicenter prospective study of an automated vulnerability safety margin system was conducted, which measured T-wave timing using an intracardiac electrogram during a ventricular pacing train. The system delivered up to 4 T-wave shocks of 18 J. Lack of VF induction by all 4 shocks was considered evidence of defibrillation adequacy. Patients subsequently underwent conventional defibrillation testing to meet a standard implant criterion. The 95% lower CI for defibrillation success at 25 J for noninduced patients was found using Bayesian statistics. Sixty patients were enrolled at 6 centers. Vulnerability testing and defibrillation success results were obtained from 54 patients. Vulnerability testing induced VF in 10 (19%) patients, of whom 2 required system revision. All patients not induced by vulnerability testing were successfully defibrillated twice at ≤25 J. The Bayesian credible interval was 97% to 100% for the population success rate of defibrillation at 25 J for automated vulnerability safety margin noninduced patients. Conclusions— An automated system identified all patients who failed conventional safety margin testing, while inducing only 19% of patients. Although limited by sample size, this study suggests the feasibility of automated implant testing that substantially reduces the need for VF induction in patients receiving implantable cardioverter-defibrillators.

Objectives To provide nursing home ( NH )‐specific estimates to assess whether venous thromboembolism ( VTE ) risk factors identified for the general population apply to NH residents. Design Population‐based case–control study. Setting O lmsted C ounty, M innesota. Participants All county residents with symptomatic objectively diagnosed incident VTE while resident in a NH from 1988 through 2000 (N = 182) and two age‐, sex‐, calendar‐year‐matched non‐ VTE O lmsted C ounty NH residents per case (N = 364). Measurements Provider‐linked medical records were reviewed to obtain information on active malignancy and recent hospitalization, surgery, trauma, or fracture as of index date (case's VTE date; respective provider registration date for controls). Risk factor prevalence and VTE ‐associated odds ratios ( OR ) were estimated and compared with previously obtained data for all O lmsted C ounty residents from 1988 through 2000. For analyses, both groups were limited to individuals aged 65 and older. Results In NH residents, active malignancy, recent hospitalization, and recent surgery significantly increased VTE risk, but the magnitude of risk appeared much lower than general population estimates (e.g., for major surgery, OR = 2.5, 95% confidence interval ( CI ) = 1.4–4.3 for NH residents vs OR = 11, 95% CI = 7.0–17 for general population). In general, the prevalence of all evaluated VTE risk factors appeared much higher in NH controls than in general population controls. Thromboprophylaxis rates appeared higher for NH cases and controls than in the general population; disconcertingly, 47% of NH cases received prophylaxis. Conclusion Although general population VTE risk factors (active cancer and recent hospitalization or surgery) can identify NH residents at higher risk for VTE , these exposures do not adequately stratify VTE risk for thromboprophylaxis recommendations. Further research into NH ‐specific risk factors and prophylaxis effectiveness is required.

Abstract —At the community level, the effect of national programs in increasing hypertension awareness, prevention, treatment, and control is unclear. This study evaluated the degree of detection and control of high blood pressure in a random population-based sample of Olmsted County, Minnesota, residents ≥45 years old, of whom 636 subjects among 1245 eligible residents agreed to participate. Home interview and home and office measurements of blood pressure were used to estimate awareness, treatment, and control rates for hypertension in the community. Mean blood pressures (±SD) were 138/80±20/12 mm Hg for men and 137/76±23/11 mm Hg for women. The overall prevalence of hypertension was 53%. The percentage of subjects with treated and controlled hypertension was 16.6%. Thirty-nine percent of subjects were unaware of their hypertension. Despite clinical trial evidence of reduced morbidity and mortality with antihypertensive therapy, recently reported national data suggest a leveling-off trend for treatment and control of hypertension. This population-based study supports these observations and suggests that at a community level, hypertension awareness and blood pressure control rates are suboptimal, presumably because of decreased attention to the detection and control of hypertension.

Atrial and brain natriuretic peptides (ANP and BNP) are produced by the heart, and their plasma concentrations are increased in human chronic congestive heart failure. Although separate studies have suggested that circulating levels of the biologically active C-terminal ANP, the biologically inactive N-terminal ANP, and BNP may have diagnostic utility in the detection of left ventricular systolic dysfunction or left ventricular hypertrophy, no studies have directly assessed the relative value of these peptides prospectively. We therefore designed this study to compare the relative ability of the different natriuretic peptides to detect abnormal left ventricular systolic and diastolic function and left ventricular hypertrophy. Using a prospective study design, we investigated 94 patients referred for cardiac catheterization and 15 age-matched normal subjects. The diagnostic abilities of elevated plasma C-terminal ANP, N-terminal ANP-(1-30), and BNP concentrations to identify systolic dysfunction (ejection fraction <45%), diastolic dysfunction (time constant of left ventricular relaxation >55 milliseconds, left ventricular end-diastolic pressure >18 mm Hg), and left ventricular hypertrophy (left ventricular mass index >120 g/m 2 ) were objectively compared by receiver operating characteristic analysis. The areas under the receiver operating characteristic curve of BNP for detecting each of these abnormalities ranged from 0.715 to 0.908 and were significantly greater than those of C-terminal ANP or N-terminal ANP-(1-30). The sensitivity and specificity of an elevated plasma BNP, which we defined as greater than the mean+3 SD of the 15 age-matched normal subjects, were 0.83 and 0.77, respectively, for detecting ejection fraction less than 45%, 0.85 and 0.70 for detecting the time constant of left ventricular relaxation greater than 55 milliseconds, 0.63 and 0.76 for detecting left ventricular end-diastolic pressure greater than 18 mm Hg, and 0.81 and 0.85 for detecting left ventricular mass index greater than 120 g/m 2 . The use of BNP and one other peptide increased sensitivity (0.90 to 0.96), albeit with lower specificity (0.56 to 0.71). An elevated plasma BNP was a more powerful marker of left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and left ventricular hypertrophy than C-terminal ANP or N-terminal ANP-(1-30) in this population of patients with suspected cardiac disease. Measurement of BNP alone or in combination with C-terminal ANP or N-terminal ANP-(1-30) has potential utility for the detection of altered left ventricular structure and function in a patient population at risk for cardiovascular disease.

Although angiotensin II (Ang II) has been implicated in the pathophysiology of congestive heart failure, its temporal and regional changes during the development and progression of the disease are poorly defined. Our objective was to assess circulating, renal, cardiac, and vascular Ang II in a canine model of rapid ventricular pacing–induced heart failure that evolves from early left ventricular dysfunction to overt congestive heart failure. Ang II was measured by radioimmunoassay with low cross-reactivity to other angiotensins. Control, early left ventricular dysfunction, and overt congestive heart failure dogs were studied. Early left ventricular dysfunction was characterized by impaired cardiac function, cardiac enlargement, preserved renal perfusion pressure, maintained urinary sodium excretion, and normal plasma renin activity. Overt congestive heart failure was characterized by further impaired cardiac function and cardiac enlargement, reduced renal perfusion pressure, urinary sodium retention, and increased plasma renin activity and plasma Ang II. In early left ventricular dysfunction dogs, renal cortical, renal medullary, ventricular, and aortic Ang II were unchanged, and atrial Ang II was decreased. In overt congestive heart failure dogs, Ang II was increased in the kidney and heart compared with normal dogs and in all tissues compared with early left ventricular dysfunction dogs. The greatest increase in tissue Ang II occurred in the renal medulla. We conclude that early increases in local renal, myocardial, and vascular Ang II do not occur in this model of early left ventricular dysfunction and may even be suppressed. In contrast, increased myocardial and particularly renal Ang II in association with increased circulating Ang II are hallmarks of overt experimental congestive heart failure. These studies provide new insights into the temporal and regional alterations in Ang II during the progression of experimental congestive heart failure.

Background —The width of the vena contracta (VC-W), the smallest area of regurgitant flow, reflects the degree of valvular regurgitation and is measurable by color Doppler imaging, but this method has not been validated in aortic regurgitation (AR). Methods and Results —We prospectively examined 79 patients with isolated AR and 80 patients without regurgitation. The VC-W was measured from the long-axis parasternal view and compared with 2 simultaneous reference methods (quantitative Doppler and 2D echocardiography). In patients without regurgitation, the agreement between methods was excellent. In patients with AR, good correlations (all P <0.0001) were obtained between VC-W and effective regurgitant orifice (ERO) area and regurgitant volume recorded by quantitative Doppler ( r =0.89 and 0.90, respectively) and 2D echocardiographic ( r =0.90 and 0.89, respectively) methods. These correlations were similar with eccentric or central jets (all P >0.60). The other methods used showed good correlations of VC-W with aortographic grading of AR (n=8, r =0.82, P =0.01), with the proximal flow convergence method (n=53, r =0.85, P <0.0001), and with left ventricular end-diastolic volume ( r =0.81, P <0.0001). Sensitivity and specificity of VC-W ≥6 mm for diagnosing severe AR (ERO ≥30 mm 2 ) were 95% and 90%, respectively. Conclusions —For assessment of the degree of AR, VC-W shows good correlations with simultaneous quantitative measures (regardless of jet direction), shows good correlations with other methods of assessment of AR, and provides a high diagnostic value for severe AR. VC-W is a simple, reliable method that can be used clinically as part of comprehensive Doppler echocardiographic assessment of AR.