Polysomnography underestimates altered cardiac autonomic control in patients with obstructive sleep apnea.

BACKGROUND: Repetitive nocturnal sympathetic activation during episodes of apnea and postapneic hyperventilation increases cardiovascular risk. The effects of hypopnea and non-apneic, non-hypopneic intervals before and after hypopnea/apnea on sympathico-vagal balance have not been assessed yet. HYPOTHESIS: Hypopnea and non-apneic, non-hypopneic intervals before and after hypopnea/apnea cause increased sympathetic activity when compared to normal respiration in nonREM stages 2­4. METHODS: A total of 34 patients were studied using in-laboratory polysomnography including continuous ECG recording. Absolute spectral power of heart rate variability in the very low (VLF), low (LF), and high frequency (HF) bands and low frequency to high frequency power ratio (LF/HF ratio) were analyzed during apnea, hypopnea, and during the pre- and post-phases of such respiratory episodes and compared to spectral powers during normal respiration in nonREM sleep 2­4. RESULTS: Patients with hypopnea and/or obstructive apnea showed higher power of VLF and the LF/HF ratio in intervals of hypopnea/apnea and in non-apneic, non-hypopneic intervals before and after hypopnea/apnea compared to normal respiration in nonREM stages 2­4. CONCLUSION: The effect of sleep-disordered breathing on alteration of autonomic tone in patients with hypopnea and obstructive apnea is more severe than estimated by conventional polysomnographic assessment of apnea and hypopnea. Patients with sleep apnea show a sympathetic overdrive not only during phases of hypopnea and obstructive apnea but also in non-apnea, non-hypopnea intervals before and after hypopnea, and obstructive apnea.

First application of a new portable, miniaturized system for extracorporeal membrane oxygenation.

Extracorporeal assist systems for respiratory and circulatory failure are increasingly used in intensive care medicine. Important technical innovations over the past years have resulted in improved biocompatibility and, consequently, reduced complication rates. Extracorporeal membrane oxygenation (ECMO) technology experienced a surge of use during the influenza A (H1N1) pandemic, but transport of unstable patients with life-threatening ARDS is still hazardous. We describe the first successful application of a newly developed, compact and easily portable ECMO device in a patient with severe ARDS due to influenza A (H1N1). Support with the miniaturized ECMO resulted in immediate improvement of gas exchange and a highly protective ventilation. Inspiratory pressure was decreased from 40 to 29 cmH(2)O and tidal volume per kilogram of predicted bodyweight could be reduced from 6.5 to 3.3 mL. Small and efficient heart-lung assist systems will become a tool of growing importance in intensive care medicine, both for profound respiratory and cardiac failure in the future. The reduced weight and compact design of the device greatly facilitates transport and handling of unstable patients on ECMO.

Quantification of left-to-right shunting in adult congenital heart disease: phase-contrast cine MRI compared with invasive oximetry.

Atrial septum defects (ASDs), ventricular septum defects (VSDs) and patent ductus arteriosus (PDA) are the most common adult congenital heart defects. The degree of left-to-right shunting as assessed by the ratio of flow in the pulmonary (Qp) and systemic circulation (Qs) is crucial in the management of these conditions. This study compared phase-contrast cine magnetic resonance imaging (PC-MRI), a non-invasive imaging technique, with invasive oximetry for the measurement of shunt volumes during cardiac catheterisation in adults with left-to-right shunting. Both invasive oximetry and shunt quantification by PC-MRI (1.5 T scanner; Sonata, Siemens Medical Solutions) were performed on 21 patients with left-to-right shunting (14 ASD, 5 VSD, 2 PDA) and data on Qp/Qs ratios and left-to-right shunt fraction compared. Mean Qp/Qs ratios assessed by PC-MRI and oximetry were 2.10+/-0.76 and 1.96+/-0.77, respectively (p = 0.37). Mean shunt fraction was 46.3+/-19.6% when calculated by PC-MRI and 42.3+/-20.1% when obtained by oximetry (p = 0.12). There was a strong correlation of Qp/Qs ratios and shunt fraction between both methods (r = 0.61, p < 0.01 and r = 0.84, p < 0.0001, respectively). The two methods had a good agreement according to Bland and Altman plots with a small but non-significant overestimation of Qp/Qs-ratios and shunt fraction by PC-MRI. On receiver operating characteristic analysis, the sensitivity and specificity of PC-MRI to detect an oximetry-derived Qp/Qs ratio of > or =1.5:1 were 93% and 100% at a PC-MRI threshold of a Qp/Qs ratio > or =1.75:1 (area under curve (AUC) = 0.99). Quantification of left-to-right shunting can be performed reliably and accurately by PC-MRI and the data obtained by this method correlate closely to those from invasive oximetry.

Safety of the novel atrial-selective K+-channel blocker AVE0118 in experimental heart failure.

Congestive heart failure (CHF) is often associated with atrial fibrillation. The safety of many antiarrhythmic drugs in CHF is limited by proarrhythmic effects. We aimed to assess the safety of a novel atrial-selective K(+)-channel blocker AVE0118 in CHF compared to a selective (dofetilide) and a non-selective IKr blocker (terfenadine). For the induction of CHF, rabbits (n = 12) underwent rapid right ventricular pacing (330-380 bpm for 30 days). AVE0118 (1 mg/kg) dofetilide (0.02 mg/kg) and terfenadine (2 mg/kg) were administered in baseline (BL) and CHF. A six-lead ECG was continuously recorded digitally for 30 min after each drug administration. At BL, dofetilide and terfenadine significantly prolonged QTc interval (218 +/- 30 ms vs 155 +/- 8 ms, p = 0.001 and 178 +/- 23 ms vs. 153 +/- 12 ms, p = 0.01, respectively) while QTc intervals were constant after administration of AVE0118 (p = n.s.). In CHF, dofetilide and terfenadine caused torsades de pointes and symptomatic bradycardia, respectively, and prolonged QTc interval (178 +/- 30 ms vs. 153 +/- 14 ms, p = 0.02 and 157 +/- 7 ms vs. 147 +/- 10 ms, p = 0.02, respectively) even at reduced dosages, whereas no QTc-prolongation or arrhythmia was observed after full-dose administration of AVE0118. In conclusion, atrial-selective K(+)-channel blockade by AVE0118 appears safe in experimental CHF.

Extracorporeal pumpless interventional lung assist in clinical practice: determinants of efficacy.

Respiratory acidosis can become a serious problem during protective ventilation of severe lung failure. A pumpless arteriovenous interventional lung assist (iLA) for extracorporeal carbon dioxide removal has been used increasingly to control critical respiratory situations. The present study sought to evaluate the factors determining the efficacy of iLA and calculate its contribution to gas exchange. In a cohort of 96 patients with severe acute respiratory distress syndrome, haemodynamic parameters, oxygen consumption and carbon dioxide production as well as gas transfer through the iLA were analysed. The measurements demonstrated a significant dependency of blood flow via the iLA device on cannula size (mean+/-sd 1.59+/-0.52 L x min(-1) for 15 French (Fr), 1.94+/-0.35 L x min(-1) for 17 Fr, and 2.22 +/-0.45 L x min(-1) for 19 Fr) and on mean arterial pressure. Oxygen transfer capacity averaged 41.7+/-20.8 mL x min(-1), carbon dioxide removal was 148.0+/-63.4 mL x min(-1). Within two hours of iLA treatment, arterial oxygen partial pressure/inspired oxygen fraction ratio increased significantly and a fast improvement in arterial carbon dioxide partial pressure and pH was observed. Interventional lung assist eliminates approximately 50% of calculated total carbon dioxide production with rapid normalisation of respiratory acidosis. Despite limited contribution to oxygen transfer it may allow a more protective ventilation in severe respiratory failure.

Increased aldosterone levels in a model of type 2 diabetes mellitus.

BACKGROUND: Aldosterone is an important mediator of cardiovascular and renal remodeling. Type II diabetes mellitus leads to renal and cardiac end organ damage. We investigated the renin-angiotensin-aldosterone system in a model of type 2 diabetes mellitus with known diabetic nephropathy and cardiac remodeling, the Zucker Diabetic Fatty rat with and without ACE-inhibition (ZDF and ZDF+ACE-I) and its control, the Zucker Lean (ZDL) rat. METHODS: Male animals were studied from an age of 7-24 weeks. At ages 7, 14, 17, 20, and 23 weeks, urinary excretion of aldosterone-glucuronide and potassium was assessed. ACE-inhibition with ramipril was started orally at week 13 (1 mg/kg/d). At the end of the study rats were sacrificed and plasma aldosterone concentration and plasma renin activity were measured. Aldosterone synthase (CYP11B2) mRNA expression in the adrenals, kidney, heart and adipose tissue was assessed by real-time PCR. Urinary albumin excretion as marker for diabetic nephropathy was measured in metabolic cages and correlated to aldosterone. RESULTS: Plasma aldosterone concentration and aldosterone-glucuronide was significantly elevated in ZDF rats, and significantly reduced by ACE-inhibiton. In contrast, plasma renin activity was significantly reduced in ZDF rats and normalized by ACE-inhibition. The urinary aldosterone correlated significantly to albuminuria. Adrenal CYP11B2 expression was not significantly higher in ZDF rats. CYP11B2 mRNA was not detected in the kidney, heart and adipose tissue. CONCLUSION: In ZDF rats, urinary and plasma aldosterone levels were elevated despite reduced plasma renin activity. The reversible effect of ACE-inhibition shows that the up-regulation of aldosterone must be dependent of the renin-angiotensin-system in this type II diabetes model. The correlation between aldosterone and diabetic nephropathy suggests a clinical relevance of this observation.

Unicuspid aortic valve disease: a magnetic resonance imaging study.

PURPOSE: Congenitally malformed aortic valves are a common finding in adults with aortic valve disease. Most of these patients have bicuspid aortic valve disease. Unicuspid aortic valve disease (UAV) is rare. The aim of our study was to describe valve morphology and the dimensions of the proximal aorta in a cohort of 12 patients with UAV in comparison to tricuspid aortic valve disease (TAV) using magnetic resonance imaging (MRI). MATERIALS AND METHODS/RESULTS: MRI studies were performed on a 1.5 T scanner in a total of 288 consecutive patients with aortic valve disease. 12 aortic valves were retrospectively classified as UAV. Annulus areas and dimensions of the thoracic aorta were retrospectively compared to a cohort of 103 patients with TAV. In UAV, valve morphology was unicuspid unicommissural with a posterior commissure in all patients. Mean annulus areas and mean diameters of the ascending aorta were significantly greater in UAV compared to TAV (12.6 +/- 4.7 cm (2) vs. 8.7 +/- 2.3 cm (2), p < 0.01 and 4.6 +/- 0.7 cm vs. 3.6 +/- 0.5 cm, p < 0.0001, respectively), while no differences were observed in the mean diameters of the aortic arch (2.3 +/- 0.6 cm vs. 2.3 +/- 0.4 cm, p = 0.69). The diameters of the descending aorta were slightly smaller in UAV compared to TAV (2.2 +/- 0.5 cm vs. 2.6 +/- 0.3 cm, p < 0.05). CONCLUSION: In UAV, visualization of valve morphology by MRI is possible with good image quality. Valve morphology was classified as unicuspid unicommissural in all UAV patients. Dilatation of the proximal aorta > 4.5 cm is a frequent finding in UAV. Additional assessment of aortic dimensions is therefore recommended in patients with UAV.

Fates of genetically engineered haematopoietic and mesenchymal stem cell grafts in normal and injured rat hearts.

There is an ongoing debate on the potential of adult stem cells as adjuvant therapy for patients with heart disease. The aim of our study was to evaluate the use of bone marrow (BM)-derived stem cells for cardiac cell and gene therapy in normal and ischaemia-injured rat hearts. Haematopoietic (HSCs) and mesenchymal stem cells (MSCs) were purified from the BM of adult rats and labelled by: (a) genetic transduction of the green fluorescent protein (GFP) using an oncoretroviral vector; (b) incorporation of the fluorescent dye PKH26 into the cell membrane; and (c) incorporation of bromodeoxyuridine into the chromosomal nucleic acid. Cells were directly injected into the beating heart (normal and shortly after coronary ligation). Retention of HSCs was--irrespective of the ischaemic injury--about 5% on day 3, and < 1% on days 10 and 28. Survival of MSCs was approximately 10-15% on day 3, but also < 5% at the later time points. Vector-mediated GFP expression was rapidly silenced after day 3. There was considerable tissue damage around the injection site. Transplanted cells did not migrate from the injection site. We did not observe phenotypical changes of the transplanted stem cells into cardiac or vascular cells.

Assessment of the anatomic regurgitant orifice in aortic regurgitation: a clinical magnetic resonance imaging study.

BACKGROUND: The aim of our study was to determine whether planimetry of the anatomic regurgitant orifice (ARO) in patients with aortic regurgitation (AR) by magnetic resonance imaging (MRI) is feasible and whether ARO by MRI correlates with the severity of AR. METHODS AND RESULTS: Planimetry of ARO by MRI was performed on a clinical magnetic resonance system (1.5 T Sonata, Siemens Medical Solutions) in 45 patients and correlated with the regurgitant fraction (RgF) and regurgitant volume (RgV) determined by MRI phase velocity mapping (PVM; MRI-RgF, MRI-RgV, n = 45) and with invasively quantified AR by supravalvular aortography (n = 32) and RgF upon cardiac catheterisation (CATH-RgF, n = 15). Determination of ARO was possible in 98% (44/45) of the patients with adequate image quality. MRI-RgF and CATH-RgF were modestly correlated (n = 15, r = 0.71, p<0.01). ARO was closely correlated with MRI-RgF (n = 44, r = 0.88, p<0.001) and was modestly correlated with CATH-RgF (n = 14, r = 0.66, p = 0.01). Sensitivity and specificity of ARO to detect moderately severe and severe aortic regurgitation (defined as MRI-RgF > or =40%) were 96% and 95% at a threshold of 0.28 cm2 (AUC = 0.99). Of note, sensitivity and specificity of ARO to detect moderately severe and severe AR at catheterisation (defined as CATH-RgF > or =40% or supravalvular aortography > or =3+) were 90% and 91% at a similar threshold of 0.28 cm2 (AUC = 0.95). Lastly, sensitivity and specificity of ARO to detect severe aortic regurgitation (defined as MRI-RgF > or =50% and/or regurgitant volume > or =60 ml) were 83% and 97% at a threshold of 0.48 cm2 (AUC = 0.97). CONCLUSIONS: Visualisation and planimetry of the ARO in patients with AR are feasible by MRI. There is a strong correlation of ARO with RgV and RgF assessed by PVM and with invasively graded AR at catheterisation. Therefore, determination of ARO by MRI is a new non-invasive measure for assessing the severity of AR.

SDF-1 expression is elevated in chronic human renal allograft rejection.

The exact mechanism of acute and chronic allograft rejection still remains unclear. The chemokine SDF-1 as mediator of allograft rejection has been under intensive investigation in liver, cardiac and bone marrow transplantation, whereas in renal transplantation, there are no reports about SDF-1 to date. This study was performed to evaluate if SDF-1 might also play an important role in human renal graft biopsies. One hundred and ninety formalin-fixed, paraffin-embedded renal allograft biopsies were included in the analysis from patients with normal renal graft morphology (according to Banff 97 classification grade 1, n = 84), with acute interstitial rejection (Banff grade 4 type I, n = 10), with acute vascular rejection (Banff grade 4 type II, n = 21), with chronic allograft nephropathy (CAN, Banff grade 5, n = 23), and without rejection but with various other lesions (Banff grade 6, n = 42). SDF-1 was localized by immunohistochemistry. In biopsies with CAN, SDF-1 expression was significantly elevated in interstitial infiltrates and infiltrating neointimal cells of arteries compared with biopsies with normal renal graft morphology. This is the first study describing a role of SDF-1 in human renal allograft rejection. We were able to demonstrate in a large number of biopsies an upregulation of SDF-1 in patients with CAN. Whether SDF-1 has pro-inflammatory or protective properties in this setting has to be evaluated in further trials.

Mechanisms of regional wall motion abnormalities in contrast-enhanced dobutamine stress echocardiography.

BACKGROUND: In the diagnosis of coronary artery disease (CAD) with Dobutamine Stress Echocardiography (DSE), regional wall motion abnormalities (RWMA) are assumed to indicate a perfusion deficit. METHODS AND RESULTS: For a more particular examination of RWMAs, we compared simultaneous echo-contrast (Optisone)-enhanced DSE (0-40 microg/kg Dobutamine, 16-segment- model) and MiBi-SPECT in a prospective double-blinded study design in 69 non-selected consecutive patients (44 male, 25 female, age 64+/-12 years). Additionally, all patients were examined by coronary-angiography. The prevalence of significant CAD (stenosis >50% lumen diameter) was 52%. DSE had a sensitivity of 78% and a specificity of 66% for the detection of significant CAD with a positive and negative predictive value of 72 and 73%, respectively. Among 28 patients with significant CAD and positive DSE study (true positive), 78% displayed a corresponding perfusion deficit in MiBi-SPECT. Among 11 patients with a positive DSE study but no current significant coronary stenosis (false positive), 82% showed stress-induced RWMAs in the inferior/posterior region, 73% displayed left ventricular hypertrophy, 54% resting-ECG abnormalities and 45% resting-RWMA (3 previous MI, 2 previous CABG surgery). Among 8 patients with negative DSE study but significant coronary stenosis (false negative), 75% had a stenosis of the LCX, 63% displayed resting- WMA, 63% displayed left bundle branch block or ST-segment depression, 50% displayed only peripheral coronary stenosis, and DSE visualization was suboptimal in 38%. CONCLUSION: This prospective study in non-selected patients shows that the majority of RWMAs in DSE are matched to a perfusion deficit detectable by nuclear imaging. Nevertheless, pre-existing cardiac abnormalities may also lead to stress-induced RWMA not associated with a perfusion deficit or mask a perfusion deficit upon DSE. Particularly in patients with LV hypertrophy, resting-RWMA, bundle branch block or ST segment depression, the predictive value of DSE may, therefore, be limited.

Effect of ACE and AT-2 inhibitors on mortality and progression to microalbuminuria in a nested case-control study of diabetic nephropathy in diabetes mellitus type 2: results from the GENDIAN study.

INTRODUCTION: There is an established role of clinical risk factors such as arterial hypertension and smoking in causing cardiovascular morbidity and diabetic nephropathy (DNP). Genetic factors increase the risk for DNP. To examine the genetic risk, we initiated a case-control study with predefined follow-up examinations. We describe the study design and baseline characteristics under special consideration of comedication, and give preliminary results of the 4-year follow-up. METHODS: We enrolled all 477 patients with DNP receiving maintenance hemodialysis in 30 centers in Southern Germany between August 1999 and January 2000. As controls, we enrolled all 482 diabetes mellitus type 2 patients without urinary microalbuminuria in two examinations on consecutive days and without other signs of renal disease in a large diabetes clinic from September 2000 to September 2001. Follow-up examinations are performed 4 and 6 years after inclusion by questionnaire and telephone interview to determine mortality and new morbidity. Controls progressing to novel DNP at follow-up, as defined by semiquantitative dipstick urinary albumin/creatinine ratio > 30 mg/g, are defined as cases in the study's nested case control component. RESULTS: At study inclusion in cases and controls, respectively, mean age was 67.3 +/- 8.2 and 58.1 +/- 11.2 years and duration of diabetes mellitus was 15.6 +/- 9.6 (at dialysis initiation) and 11.0 +/- 8.6 years. 328 controls (of which 25 had died and 14 did not perform urinalysis) were subjected to follow-up at 4 years, at a mean of 3.5 +/- 0.8 years after inclusion. 51.2% (n = 148) of living controls remained normalbuminuric, 33.9% (n = 98) had microor macroalbuminuria, and in 14.9% (n = 43) the dipstick test was inconclusive. There was no significant difference in progression to micro- or macroalbuminuria between controls treated with ACE or AT-2 inhibitors at baseline or not. Renal function as estimated by the abbreviated MDRD formula declined from 86.8 +/- 21.0 to 82.5 +/- 22.3 ml/min/1.73 m2 (p < 0.001). The decline was significant in patients on ACE or AT-2 inhibitors at baseline and not in patients without such medication at baseline. DISCUSSION: GENDIAN is a large case-control study designed to evaluate clinical and genetic determinants of DNP and other complications of long-standing diabetes mellitus type 2. We observed an association of ACE or AT-2 inhibitor therapy with cardiovascular comorbidity and a significant decline in renal function after a 4-year follow-up.

MRI planimetry for diagnosis and follow-up of valve area in mitral stenosis treated with valvuloplasty.

PURPOSE: We sought to determine whether noninvasive planimetry by magnetic resonance imaging (MRI) is suitably sensitive and reliable for visualizing the mitral valve area (MVA) and for detecting increases in the MVA after percutaneous balloon mitral valvuloplasty (PBMV). MATERIALS AND METHODS: In 8 patients with mitral valve stenosis, planimetry of the MVA was performed before and after PBMV with a 1.5 T MR scanner using a breath-hold balanced gradient echo sequence (True FISP). The data was compared to the echocardiographically determined MVA (ECHO-MVA) as well as to the invasively calculated MVA by the Gorlin formula at catheterization (CATH-MVA). RESULTS: PBMV was associated with an increase of 0.79 +/- 0.30 cm (2) in the MVA (Delta MRI-MVA). The correlation between Delta MRI-MVA and Delta CATH-MVA was 0.92 (p < 0.03) and that between Delta MRI-MVA and Delta ECHO-MVA was 0.90 (p < 0.04). The overall correlation between MRI-MVA and CATH-MVA was 0.95 (p < 0.0001) and that between MRI-MVA and ECHO-MVA was 0.98 (p < 0.0001). MRI-MVA slightly overestimated CATH-MVA by 8.0 % (1.64 +/- 0.45 vs. 1.51 +/- 0.49 cm (2), p < 0.01) and ECHO-MVA by 1.8 % (1.64 +/- 0.45 vs. 1.61 +/- 0.43 cm (2), n. s.). CONCLUSION: Magnetic resonance planimetry of the mitral valve orifice is a sensitive and reliable method for the noninvasive quantification of mitral stenosis and visualization of small relative changes in the MVA. This new method is therefore capable of diagnosing as well as following the course of mitral stenosis. It must be taken into consideration that planimetry by MRI slightly overestimates the MVA as compared to cardiac catheterization.

Exanthema and acute anuric renal failure.

A 15-year-old girl with a history of Kawasaki disease was admitted to our nephrological department due to acute renal failure. Despite antibiotic therapy because of fever and the symptoms of a pharyngitis in the last few days, the girl showed persisting fever and developed arthralgias, an exanthema and a rising serum creatinine as well as anuria. A wide variety of differential diagnoses has to be thought of because of the history of the Kawasaki disease (symptoms like fever, pharyngitis, exanthema and arthralgia), i.e. hemolytic-uremic syndrome, vasculitis, ascending infection, postinfection glomerulonephritis. In consideration of etiologically unclear "rapidly progressive renal failure" with anuria and thrombocytopenia an immediate renal biopsy was done and revealed a severe drug induced acute interstitial nephritis. Due to this diagnosis we treated the patient with corticosteroids. Within 4 weeks serum creatinine declined to 1.8 mg/dl but did not normalize.

Delayed hyperenhancement in magnetic resonance imaging of left ventricular hypertrophy caused by aortic stenosis and hypertrophic cardiomyopathy: visualisation of focal fibrosis.

OBJECTIVE: To compare the extent and distribution of focal fibrosis by gadolinium contrast-enhanced magnetic resonance imaging (MRI; delayed hyperenhancement) in severe left ventricular (LV) hypertrophy in patients with pressure overload caused by aortic stenosis (AS) and with genetically determined hypertrophic cardiomyopathy (HCM). METHODS: 44 patients with symptomatic valvular AS (n = 22) and HCM (n = 22) were studied. Cine images were acquired with fast imaging with steady-state precession (trueFISP) on a 1.5 T scanner (Sonata, Siemens Medical Solutions). Gadolinium contrast-enhanced MRI was performed with a segmented inversion-recovery sequence. The location, extent and enhancement pattern of hyperenhanced myocardium was analysed in a 12-segment model. RESULTS: Mean LV mass was 238.6 (SD 75.3) g in AS and 205.4 (SD 80.5) g in HCM (p = 0.17). Hyperenhancement was observed in 27% of patients with AS and in 73% of patients with HCM (p < 0.01). In AS, hyperenhancement was observed in 60% of patients with a maximum diastolic wall thickness >or= 18 mm, whereas no patient with a maximum diastolic wall thickness < 18 mm had hyperenhancement (p < 0.05). Patients with hyperenhancement had more severe AS than patients without hyperenhancement (aortic valve area 0.80 (0.09) cm(2)v 0.99 (0.3) cm(2), p < 0.05; maximum gradient 98 (22) mm Hg v 74 (24) mm Hg, p < 0.05). In HCM, hyperenhancement was predominant in the anteroseptal regions and patients with hyperenhancement had higher end diastolic (125.4 (36.9) ml v 98.8 (16.9) ml, p < 0.05) and end systolic volumes (38.9 (18.2) ml v 25.2 (1.7) ml, p < 0.05). The volume of hyperenhancement (percentage of total LV myocardium), where present, was lower in AS than in HCM (4.3 (1.9)% v 8.6 (7.4)%, p< 0.05). Hyperenhancement was observed in 4.5 (3.1) and 4.6 (2.7) segments in AS and HCM, respectively (p = 0.93), and the enhancement pattern was mostly patchy with multiple foci. CONCLUSIONS: Focal scarring can be observed in severe LV hypertrophy caused by AS and HCM, and correlates with the severity of LV remodelling. However, focal scarring is significantly less prevalent in adaptive LV hypertrophy caused by AS than in genetically determined HCM.

Cardiovascular phenotypes and functional parameters in the general population--results of the MONICA/KORA studies.

The MONICA/KORA surveys are characterized by a careful and broad investigation of multiple cardiovascular phenotypes. Particularly, repeated blinded measurements of blood pressure, comprehensive echocardiographic and electrocardiographic evaluations as well as differentiation between fat and fat-free body mass have led to manifold innovative observations. Specifically, genetic and serological markers of the renin angiotensin system could be associated with high blood pressure and left ventricular hypertrophy. The same applies to the importance of parameters of body composition as obesity and muscular mass. Moreover, the prevalence of heart failure in the general population could be determined for the first time in Germany. Additionally, the prevalence of left ventricular systolic and diastolic dysfunction could be obtained in the region of the survey, exemplarily for the Federal Republic of Germany. Finally, the surveys of the population random sample were used to define normal serum levels of natriuretic peptides. In summary, the evaluation of cardiovascular phenotypes in the MONICA/KORA surveys resulted in a -- in the European region unique -- documentation of cardiovascular functional parameters in the general population. Moreover, multiple epidemiological observations as to pathophysiologically relevant topics of heart and vascular diseases could be studied in extraordinary details.

Effect of HMG-CoA-reductase inhibitors on survival in type 2 diabetes patients with end stage diabetic nephropathy.

INTRODUCTION: We studied the effect of HMG-CoA-reductase inhibitor (= CSE-I) treatment on mortality in a population of hemodialysis patients with diabetic nephropathy due to type 2 diabetes. Since the efficacy of CSE-I in dialysis patients is discussed controversially, we tested the hypothesis that only patients with LDL-cholesterol > 100 mg/dl benefit from CSE-I. METHODS: We enrolled all 445 prevalent chronic hemodialysis patients with end-stage diabetic nephropathy from 30 centres in Southern Germany from August 1999 to January 2000 for prospective study until December 2003. Fasting lipid profiles prior to dialysis session and a complete clinical phenotype were determined at inclusion. We formed 2 patient groups (serum LDL > vs. < or = 100 mg/dl). Only CSE-I were used as lipid lowering therapy in our cohort. 122 Patients were on CSE-I therapy during the study. All cause mortality (ACM) was the primary end point. Survival analysis was performed by Kaplan Meier and multivariate Cox regression analysis. RESULTS: Multivariate regression analysis and Kaplan Meier survival analysis showed a decrease in risk for ACM for patients on CSE-I therapy, irrespective of lipid status (multivariate hazard ratio (= HR) 0.58; p = 0.049; ACM 72.1% (no CSE-I) vs. 59.7% (+ CSE-I); mean survival 2.37 +/- 0.08 years (no CSE-I) vs. 2.77 +/- 0.12 years (+ CSE-I), p = 0.003). In patients with LDL > 100 mg/dl, statin treatment was also associated with reduced ACM: 48.0% (+ CSE-I) vs. 70.1% (no CSE-I), (multivariate HR 0.28, CI 95% 0.11 - 0.75, p = 0.01), but not in patients with LDL < or = 100 mg/dl (HR 0.84, CI 95% 0.41 - 1.72 p = 0.63). CONCLUSION: Our data indicates that hemodialysis patients with type 2 diabetic nephropathy may benefit from statin therapy irrespective of baseline LDL-cholesterol level. Patients with LDL > 100 mg/dl benefit most when treated with CSE-I.

Effect of genetic variation on therapy with angiotensin converting enzyme inhibitors or angiotensin receptor blockers in dialysis patients.

INTRODUCTION: The role of interaction of polymorphisms in the Renin-Angiotensin-System (RAS) with angiotensin converting enzyme (ACE) or angiotensin receptor (AGTR1) inhibitors (RAS inhibitors) is unknown, as is the role of such therapy in end stage renal disease (ESRD) patients. METHODS: We enrolled all 445 prevalent patients with diabetic nephropathy receiving maintenance hemodialysis in 30 centers in Southern Germany from August 1999 to January 2000 for prospective survival analysis until December 2003. Blood pressure and medication was recorded at inclusion. We determined survival specific for allelic variants of the ACE (insertion/deletion), Angiotensinogen (M235T) and AGTR1 (A1166C) genes. The effect of therapy with RAS inhibitors at study inclusion was determined for the allelic variants of each gene. The primary end point was all cause mortality (ACM). RESULTS: For all polymorphisms, and for therapy with RAS inhibitors there was no significant effect on survival in the complete collective (n = 445), though there was an insignificant trend for improved survival in patients on AGTR1 antagonists. Increased ACM risk was associated with treatment with RAS inhibitors only in patients homozygous for the wild type AGTR1 1166A allele (HR 1.65, p = 0.01). For all other polymorphisms, therapy with RAS inhibitors had no significant effect on ACM, irrespective of genotype. Similar results were obtained in patients with systolic ventricular dysfunction. CONCLUSION: Our data do not show a survival advantage for type 2 diabetes hemodialysis patients receiving RAS inhibiting therapy. In addition, our data indicate that allelic variation in RAS genes and pharmacogenetic interaction with RAS inhibition does not affect mortality risk in diabetic hemodialysis patients.

BNP as a marker of diastolic dysfunction in the general population: Importance of left ventricular hypertrophy.

BNP is a marker of systolic left ventricular dysfunction (LVSD) and heart failure. To assess BNP for the detection of diastolic dysfunction in the general population, we examined 1678 subjects within an age- and sex-stratified survey (MONICA Augsburg). BNP was measured using a commercially available RIA (Shionogi). BNP increased in subjects with diastolic dysfunction (mean 20.3+/-4.7 pg/ml vs. control 9.6+/-0.5 pg/ml, p<0.001), but to a lesser extent than in subjects with LV hypertrophy (LVH, mean 37.3+/-49.1 pg/ml, p<0.001 vs. control) or LVSD (mean 76.2+/-23.2 pg/ml, p<0.001 vs. control). Individuals with sole diastolic abnormality displayed BNP concentrations at the control level (mean 9.7+/-1.7 pg/ml). In univariate analysis, age, BMI, systolic blood pressure, left atrial size, LV mass index, diastolic dysfunction and EF displayed a significant correlation with BNP (p<0.001). However, LV mass index displaced diastolic dysfunction as a significant predictor of BNP in multivariate analysis. Upon ROC analysis, sensitivity and specificity for the detection of diastolic dysfunction by BNP were only 61% and 55%, respectively. Nevertheless, a normal BNP test virtually excluded the presence of diastolic dysfunction and concomitant LVH (NPV 99.9%). Increased BNP concentrations in subjects with diastolic dysfunction are strongly related to LVH. Population-wide screening for diastolic dysfunction with BNP cannot be recommended although a normal BNP test usually excludes diastolic dysfunction and LV hypertrophy.