Nicole Heussen

Sustained Benefits in Vascular Function Through Flavanol-Containing Cocoa in Medicated Diabetic Patients: A Double-Masked, Randomized, Controlled Trial

OBJECTIVES Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients. BACKGROUND Even in fully medicated diabetic patients, overall prognosis is unfavorable due to deteriorated cardiovascular function. Based on epidemiological data, diets rich in flavanols are associated with a reduced cardiovascular risk. METHODS In a feasibility study with 10 diabetic patients, we assessed vascular function as flow-mediated dilation (FMD) of the brachial artery, plasma levels of flavanol metabolites, and tolerability after an acute, single-dose ingestion of cocoa, containing increasing concentrations of flavanols (75, 371, and 963 mg). In a subsequent efficacy study, changes in vascular function in 41 medicated diabetic patients were assessed after a 30-day, thrice-daily dietary intervention with either flavanol-rich cocoa (321 mg flavanols per dose) or a nutrient-matched control (25 mg flavanols per dose). Both studies were undertaken in a randomized, double-masked fashion. Primary and secondary outcome measures included changes in FMD and plasma flavanol metabolites, respectively. RESULTS A single ingestion of flavanol-containing cocoa was dose-dependently associated with significant acute increases in circulating flavanols and FMD (at 2 h: from 3.7 +/- 0.2% to 5.5 +/- 0.4%, p < 0.001). A 30-day, thrice-daily consumption of flavanol-containing cocoa increased baseline FMD by 30% (p < 0.0001), while acute increases of FMD upon ingestion of flavanol-containing cocoa continued to be manifest throughout the study. Treatment was well tolerated without evidence of tachyphylaxia. Endothelium-independent responses, blood pressure, heart rate, and glycemic control were unaffected. CONCLUSIONS Diets rich in flavanols reverse vascular dysfunction in diabetes, highlighting therapeutic potentials in cardiovascular disease.

Strain rate measurement by Doppler echocardiography allows improved assessment of myocardial viability in patients with depressed left ventricular function

OBJECTIVES This study sought to evaluate whether objective assessment of the myocardial functional reserve, using strain rate imaging (SRI), allows accurate detection of viable myocardium. BACKGROUND Strain rate imaging is a new echocardiographic modality that allows quantitative assessment of segmental myocardial contractility. METHODS In 37 patients (age 58 +/- 9 years) with ischemic left ventricular dysfunction, myocardial viability was assessed using low-dose (10 microg/kg body weight per min) two-dimensional dobutamine stress echocardiography (DSE), tissue Doppler imaging, SRI and (18)F-fluorodeoxyglucose ((18)FDG) positron emission tomography (PET). The peak systolic tissue Doppler velocity and peak systolic myocardial strain rate were determined at baseline and during low-dose dobutamine stress from the apical views. RESULTS A total of 192 segments with dyssynergy at rest were classified by (18)FDG PET as viable in 94 and nonviable in 98. An increase of peak systolic strain rate from rest to dobutamine stimulation by more than -0.23 1/s allowed accurate discrimination of viable from nonviable myocardium, as determined by (18)FDG PET with a sensitivity of 83% and a specificity of 84%. Receiver operating characteristic (ROC) curve analysis showed an area under the curve for prediction of nonviable myocardium, as determined by (18)FDG PET using SRI, of 0.89 (95% confidence interval [CI] 0.88 to 0.90), whereas the area under the ROC curve using tissue Doppler imaging was 0.63 (95% CI 0.61 to 0.65). CONCLUSIONS The increase in the peak systolic strain rate during low-dose dobutamine stimulation allows accurate discrimination between different myocardial viability states. Strain rate imaging is superior to two-dimensional DSE and tissue Doppler imaging for the assessment of myocardial viability.

Prospective 10‐year Follow‐up in Adolescent Anorexia Nervosa—Course, Outcome, Psychiatric Comorbidity, and Psychosocial Adaptation

The aim of the present study was to follow up the long-term course of adolescent-onset anorexia nervosa by repeated assessment, to analyze the association between the course of the eating disorder and psychiatric comorbidity, and to evaluate psychosocial outcome. The sample consisted of 39 inpatients who were reinvestigated 3, 7, and 10 years after discharge. The patients and 39 controls matched for age, gender, and occupational status were assessed with structured interviews on DSM-III-R eating disorders, additional axis I and axis II psychiatric disorders, and psychosocial functioning. Results showed that 69 % of the original subjects met the criteria for full recovery at the 10-year follow-up. One patient (3%) still exhibited the full syndrome of restrictive anorexia nervosa, two patients (5%) the full syndrome of bulimia nervosa. None of the patients had died. Of the subjects, 51% currently had an axis I psychiatric disorder and 23% met the full criteria for a personality disorder. Apart from the eating disorder, anxiety disorders and avoidant-dependent and obsessive-compulsive personality disorders were the most common psychiatric diagnoses. There was a significant association between psychiatric comorbidity and the outcome of the eating disorder and between outcome and psychosocial adaptation. With regard to psychiatric morbidity and psychosocial functioning, long-term recovered patients did not differ significantly from normal controls. It is concluded that in most patients adolescent anorexia nervosa takes a prolonged course, although it seems to be more favorable than in adult-onset forms. Those who achieve complete recovery from the eating disorder have a good chance of overcoming other psychiatric disorders and to adapt to social requirements.

Myocardial viability in chronic ischemic heart disease: Comparison of contrast-enhanced magnetic resonance imaging with 18F-fluorodeoxyglucose positron emission tomography

OBJECTIVES We sought to compare contrast-enhanced magnetic resonance imaging (ceMRI) with nuclear metabolic imaging for the assessment of myocardial viability in patients with chronic ischemic heart disease and left ventricular (LV) dysfunction. BACKGROUND Contrast-enhanced MRI has been shown to identify scar tissue in ischemically damaged myocardium. METHODS Twenty-six patients with chronic coronary artery disease and LV dysfunction (mean ejection fraction 31 +/- 11%) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET), technetium-99m tetrofosmin single-photon emission computed tomography (SPECT), and ceMRI. In a 17-segment model, the segmental extent of hyperenhancement (SEH) by ceMRI, defined as the relative amount of contrast-enhanced tissue per myocardial segment, was compared with segmental FDG and tetrofosmin uptake by PET and SPECT. RESULTS In severely dysfunctional segments (n = 165), SEH was 9 +/- 14%, 33 +/- 25% (p < 0.05), and 80 +/- 23% (p < 0.05) in segments with normal metabolism/perfusion, metabolism/perfusion mismatch, and matched defects, respectively. Segmental glucose uptake by PET was inversely correlated to SEH (r = -0.86, p < 0.001). By receiver operator characteristic curve analysis, the area under the curve was 0.95 for the differentiation between viable and non-viable segments. At a cutoff value of 37%, SEH optimally differentiated viable from non-viable segments defined by PET. Using this threshold, the sensitivity and specificity of ceMRI to detect non-viable myocardium as defined by PET were 96% and 84%, respectively. CONCLUSIONS Contrast-enhanced MRI allows assessment of myocardial viability with a high accuracy, compared with FDG-PET, in patients with chronic ischemic heart disease and LV dysfunction.

Prediction of clinical outcome after mechanical revascularization in acute myocardial infarction by markers of myocardial reperfusion

OBJECTIVES We sought to evaluate and compare recently suggested parameters of reperfusion after angioplasty in acute myocardial infarction (AMI) for risk stratification during long-term follow-up. BACKGROUND Abnormal myocardial perfusion has a detrimental impact on survival. Several parameters of reperfusion have been evaluated in controlled study populations for risk stratification. METHODS In 253 consecutive patients undergoing intervention in AMI on a native coronary vessel, angiographic myocardial blush grade (MBG), corrected TIMI (thrombolysis in myocardial infarction) frame count (CTFC) and persistent ST-segment elevation (STE) were determined to evaluate reperfusion. This was a high-risk population, including referral for treatment failure at a primary center in 29.2%, failed thrombolysis in 22.1% and cardiogenic shock in 13.4% of cases. RESULTS In addition to age, patient referral, LBBB and heart rate on admission, MBG 0 to 1 (odds ratio [OR] = 3.23, p < 0.001), CTFC (OR = 1.01, p = 0.015) and persistent STE >2 leads (OR = 3.46, p = 0.010) were univariate predictors of mortality during a 22.1 +/- 15.6 months follow-up. Myocardial blush grade 0 to 1 (OR = 2.17, p = 0.033) and persistent STE (OR = 3.61, p = 0.017) persisted as independent predictors of mortality, whereas CTFC failed. Differences in mortality between reperfusion groups at 30 days remained throughout the complete follow-up. In sequential Cox models, the predictive power of clinical data alone for mortality (model chi-squared 55.8) was strengthened by adding MBG (model chi-squared 64.2) and ECG postintervention (model chi-squared 69.2). CONCLUSIONS Myocardial blush grade 0 to 1 and persistent STE are independent predictors for long-term mortality after angioplasty in AMI. Corrected TIMI frame count is a less powerful predictor. Combining both parameters to consider quality of reperfusion in the myocardium at risk and extent of the infarct zone increases the predictive power.

Survival probability of zirconia-based fixed dental prostheses up to 5 yr: a systematic review of the literature.

The purpose of this systematic review was to calculate the 5-yr survival rates of all-ceramic zirconia-based fixed dental prostheses (FDPs) and to analyze technical and biological complications. An electronic literature search of MEDLINE (PubMed) was conducted independently by three reviewers to identify clinical studies from 1999 to 2009 and was completed by a manual search. Keywords and inclusion and exclusion criteria were well-defined. The search revealed 399 titles and led to the final analysis of 18 full-text articles. Nine studies met the inclusion criteria. Extracted data were statistically calculated into 5-yr survival rates and 5-yr complication-free rates by using Poisson regression analysis. In total, 310, 3- to 4-unit FDPs and 20 FDPs with more than 4 units were included. The estimated 5-yr survival rate for all FDPs was 94.29% (95% CI: 58.98-99.32); 19 FDPs were lost as a result of catastrophic failures. The 5-yr complication-free rate regarding technical complications was 76.41% (95% CI: 42.42-91.60) with chipping being the most frequent complication. Regarding biological complications, the 5-yr complication-free rate was 91.72% (95% CI: 59.19-98.53). The survival rates of zirconia-based short-unit FDPs are promising. However, an important improvement of the veneering systems is required, and for FDPs with more units in function, further randomized, controlled clinical trials are necessary.

Intracoronary infusion of autologous bone marrow cells and left ventricular function after acute myocardial infarction: a meta-analysis

Recent clinical studies have demonstrated that intracoronary infusion of autologous bone marrow cells (BMC) in conjunction with standard treatment may improve left ventricular function after an acute myocardial infarction (AMI). However, the results of these studies remain controversial, as the studies were relatively small in size and partially differed in design. We reviewed primary controlled randomized clinical studies comparing intracoronary transfer of autologous non‐mobilized BMC combined with standard therapy versus standard therapy alone in patients with AMI. We identified five randomized controlled clinical trials, three of which were also placebo‐ and bone marrow aspiration‐controlled. Non‐mobilized BMC were infused into the revascularized coronary target artery 6.6 ± 6.1 days after AMI. The mean follow‐up period of 5.2 ± 1.1 months was completed by 482 patients, 241 of which received infusion of BMC. The effect of BMC on left ventricular ejection fraction (LVEF) as a major functional parameter was evaluated. Analyzing the overall effect on the change in LVEF between baseline and follow‐up value revealed a significant improvement in the BMCtreated group as compared to the control group (P = 0.04). Thus, considering the increase in LVEF during follow‐up, transplantation of BMC may be a safe and beneficial procedure to support treatment of AMI. However, the functional improvement observed with this form of therapy was altogether relatively moderate and the studies were heterogeneous in design. Hence, further efforts aiming at large‐scale, double‐blind, randomized and placebo‐controlled multi‐center trials in conjunction with better definition of patients, which benefit from BMC infusion, appear to be warranted.

Clinical study: cardiac imagingMyocardial viability inchronic ischemic heart disease: Comparison of contrast-enhanced magnetic resonance imaging with 18F-fluorodeoxyglucose positron emission tomography

OBJECTIVES We sought to compare contrast-enhanced magnetic resonance imaging (ceMRI) with nuclear metabolic imaging for the assessment of myocardial viability in patients with chronic ischemic heart disease and left ventricular (LV) dysfunction. BACKGROUND Contrast-enhanced MRI has been shown to identify scar tissue in ischemically damaged myocardium. METHODS Twenty-six patients with chronic coronary artery disease and LV dysfunction (mean ejection fraction 31 +/- 11%) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET), technetium-99m tetrofosmin single-photon emission computed tomography (SPECT), and ceMRI. In a 17-segment model, the segmental extent of hyperenhancement (SEH) by ceMRI, defined as the relative amount of contrast-enhanced tissue per myocardial segment, was compared with segmental FDG and tetrofosmin uptake by PET and SPECT. RESULTS In severely dysfunctional segments (n = 165), SEH was 9 +/- 14%, 33 +/- 25% (p < 0.05), and 80 +/- 23% (p < 0.05) in segments with normal metabolism/perfusion, metabolism/perfusion mismatch, and matched defects, respectively. Segmental glucose uptake by PET was inversely correlated to SEH (r = -0.86, p < 0.001). By receiver operator characteristic curve analysis, the area under the curve was 0.95 for the differentiation between viable and non-viable segments. At a cutoff value of 37%, SEH optimally differentiated viable from non-viable segments defined by PET. Using this threshold, the sensitivity and specificity of ceMRI to detect non-viable myocardium as defined by PET were 96% and 84%, respectively. CONCLUSIONS Contrast-enhanced MRI allows assessment of myocardial viability with a high accuracy, compared with FDG-PET, in patients with chronic ischemic heart disease and LV dysfunction.

Depression, anxiety, and obsessionality in long-term recovered patients with adolescent-onset anorexia nervosa

Anorexia nervosa (AN) is frequently associated with symptoms of depression, anxiety, and obsessive-compulsive behavior which also develop secondary to semistarvation. It is less certain if these symptoms persist after recovery. A few studies have already reported on high prevalence rates of anxious, depressive, and obsessive features in long-term recovered patients with AN, but several of these so called “long-term” recovered patients had only maintained weight restoration for six to twelve months. The aim of this study was to determine whether depressive, anxious, and obsessive-compulsive symptoms persist in truly long-term recovered patients (BMI 20.3±2.5 kg/m2) who no longer had any eating disorder symptoms (including weight phobia) for at least 3 years. Seventeen subjects of an AN sample (n=39) previously described in a 10-year follow-up met our strict criteria of at least 3 years of complete recovery of AN. In comparison to 39 age-, sex-, and occupation-matched healthy subjects without a history of psychiatric or eating disorder, long-term recovered patients had higher levels of depressive (p=0.002), anxious (p=0.006), and obsessive-compulsive (p=0.015) features but did not differ with regard to psychiatric morbidity and psychosocial adaptation. In conclusion, depressive, anxious, and obsessive-compulsive symptoms may be personality traits in subjects with former adolescent anorexia nervosa.

High serum leptin levels subsequent to weight gain predict renewed weight loss in patients with anorexia nervosa

It has repeatedly been shown that high serum leptin levels at target weight ensue from therapeutically induced weight gain in patients with anorexia nervosa (AN). It was hypothesized that elevated leptin levels may be an important factor underlying the difficulties of maintaining the target-weight in AN patients after re-feeding. The aim of this study was to examine if serum leptin levels at discharge from inpatient treatment predict renewed weight loss within 2 months after discharge and upon a 1 yr follow-up. Univariate variance analysis (ANOVA) revealed that 60% (cor. R2=0.60, P=0.002) of the variance in the BMI standard deviation score (BMI-SDS) 2 months after discharge was explained by the model consisting of the independent variables lg10 leptin levels at discharge (P=0.019) and at admission (P=0.069) and BMI-SDS at admission (P=0.002) and delta BMI between admission and discharge (P=0.047). Similarly, 60% (cor. R2=0.60, P=0.005) of the variance in BMI-SDS 1 yr after discharge was explained by lg10 leptin levels at discharge (P=0.046) and at admission (P=0.052) and BMI-SDS at admission (P=0.008) and 2 months after discharge (P=0.007) and delta BMI between admission and discharge (P=0.933). Patients with a poor outcome after 1 yr (n=9, ANCOVA, group: descriptive P=0.041), but not recovered patients (n=9, P=0.649), had lg10 leptin levels at discharge higher than those of controls when adjusted for BMI and % body fat at discharge. In conclusion, high serum leptin levels at discharge from inpatient treatment may indicate a risk for renewed weight loss and an unfavorable 1 yr outcome in AN.