Frank Weidemann - Academia.edu (original) (raw)

Papers by Frank Weidemann

European Journal of Clinical Investigation, 2008

Signs and symptoms of classic Fabry disease manifest itself on the skin (angiokeratoma), the nerv... more Signs and symptoms of classic Fabry disease manifest itself on the skin (angiokeratoma), the nervous system (acroparaesthesia), the heart (restrictive cardiomyopathy) and a variety of other organs. Diagnosis of Fabry disease was confirmed by genetic tests in a cohort of 100 patients and a standardized examination programme was performed in all patients. We were puzzled when applying well-established and textbook-anchored signs and symptoms to our patients. Among the 47 male and 53 female patients (mean age 41 +/- 16 years) with genetically proven disease, the Fabry-type vascular skin lesions were without hyperkeratotic aspect and keratomas were virtually absent. The peripheral neuropathic pain found in all male patients was not compatible with the wording 'acro' and 'paraesthesia', suggesting a different pathophysiological mechanism. Upon echocardiographic examination, patients mainly revealed diastolic relaxation abnormalities of the heart and only one patient had a restrictive cardiac pattern. Our findings suggest that some terms used to describe signs and symptoms of Fabry disease are historically derived and do not comply with state-of-the-art examination. We propose to replace the term 'angiokeratoma' with 'angioma', the term 'acroparaesthesia' with 'neuropathic pain' and the term 'restrictive cardiomyopathy' with 'cardiac hypertrophic storage disease'. As most of the physicians are not familiar with Fabry disease, terms used in the past might prevent the correct diagnosis of a potentially treatable disease.

Kidney International, 2003

Fabry disease: Diagnosis and treatment. Fabry disease is an X-linked lysosomal storage disorder t... more Fabry disease: Diagnosis and treatment. Fabry disease is an X-linked lysosomal storage disorder that results from a deficiency of the enzyme α-galactosidase A (α-Gal A). The lack of α-Gal A causes an intracellular accumulation of glycosphingolipids, mainly globotriaosyceramide (GL3). Affected organs include, among others, the vascular endothelium, heart, brain, and kidneys, leading to end-stage renal disease (ESRD). Since Fabry disease

Pediatric Cardiology, 2002

From a temporally resolved radio-frequency data set, a series of new developing indices of region... more From a temporally resolved radio-frequency data set, a series of new developing indices of regional myocardial deformation can be measured. These may be important new data sets to quantify regional radial and long axis function of the left or right ventricle in children with acquired or congenital heart disease. Using color Doppler methodology unidimensional regional myocardial strain rates (SR) and natural strain (e) can now be calculated from local myocardial velocity data sets. Normal regional velocity, SR, and e values have already been determined in older children and should form the database for studies into acquired or congenital heart disease in this age group. Neonatal and infant values have yet to be determined. This article will present preliminary data on the potential clinical value of ultrasonic regional SR and e imaging in children and will discuss the close interrelation of these new regional function parameters with an alternative approach to quanti®cation: the measurement of local cyclical changes in integrated backscatter levels.

World journal of cardiology, Jan 26, 2015

We are reporting a long-time magnetic resonance imaging (MRI) follow-up in a rare case of cardiac... more We are reporting a long-time magnetic resonance imaging (MRI) follow-up in a rare case of cardiac left lateral wall hypertrophy. Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder and a significant cause of sudden cardiac death. Cardiac magnetic resonance (CMR) imaging can be a valuable tool for assessment of detailed information on size, localization, and tissue characteristics of hypertrophied myocardium. However, there is still little knowledge of long-term evolution of HCM as visualized by magnetic resonance imaging. Recently, our group reported a case of left lateral wall HCM as a rare variant of the more common forms, such as septal HCM, or apical HCM. As we now retrieved an old cardiac MRI acquired in this patient more than 20 years ago, we are able to provide the thrilling experience of an ultra-long MRI follow-up presentation in this rare case of left lateral wall hypertrophy. Furthermore, this case outlines the tremendous improvements in i...

Objective: The long-term effects and mechanisms of early started angiotensin converting enzyme (A... more Objective: The long-term effects and mechanisms of early started angiotensin converting enzyme (ACE) inhibition post myocardial infarction (MI) are not well understood. Chronic effects of early ACE inhibition on hemodynamics, left ventricular diastolic wall stress and remodeling were, therefore, compared to that of angiotensin AT -receptor subtype blockade in rats with experimental myocardial 1 infarction. The contribution of bradykinin potentiation

European Journal of Echocardiography, 2006

ABSTRACT Background: In patients with Fabry disease enzyme replacement therapy (ERT) has been sho... more ABSTRACT Background: In patients with Fabry disease enzyme replacement therapy (ERT) has been shown to decrease left ventricular (LV) hypertrophy. Whether these results are valid for patients in different stages of the disease has yet to be demonstrated. Methods: 45 Fabry patients who were treated with 1.0 mg/kg body weight of recombinant a-Gal A (agalsidase ß, Fabrazyme®) were followed for up to three years by echocardiography. LV end-diastolic wall thicknesses of the posterior wall were measured by M-mode echocardiography. In addition, LV end-diastolic and end-systolic diameters were extracted. Results: Patients were divided in three groups according to their end-dias-tolic wall thickness before starting ERT. Group 1: Patients with no LV hyper-trophy (wall thickness <11.5 mm; n=18; mean age 34±11 yrs). These pa-tients stayed non-hypertrohic in the 3 years follow-up during ERT. Group 2: Patients with mild LV hypertrophy (wall thickness between 11.5 and 13.5 mm; n=16; mean age 43±9 yrs). LV wall thickness decreased after 1 year and normalized in the 3 years follow-up period. Group 3: Patients with severe LV hypertrophy (wall thickness >13.5 mm; n=11; mean age 50±10 yrs). In these patients wall thickness decreased after one year of ERT significantly. How-ever, there was no further change up to 3 years and they remained hyper-trophic. (Figure) LV diameters were normal in the 3 groups and did not change during ERT. Conclusions: In Fabry cardiomyopathy, especially patients without or with only mild initial hypertrophy seem to benefit from long term enzyme replace-ment therapy. Background: The cause of fluctuations in the cardiac troponins in patients with renal failure overtime is exactly unclear. The aim of this study was to evaluate the relationship between the increase of LVMI and the fluctuations in the cardiac troponins at the follow up. Methods: Totally 110 patients (50 women, 60 men, mean age: 43±14 years) with end-stage renal disease were included in present study. Baseline echo-cardiography and troponin assays were performed. Follow-up echocardio-graphy and troponin assays were also performed after 18.2±2.2 (14-23) month. Results: At the baseline, troponin T (cTnT) was positive in 19 (17%) of pa-tients, negative in 91 (83%) of patients. Troponin I (cTnI) was positive in 27 (25%) of patients, negative in 83 (75%) of patients. After the follow-up, cTnT was positive in 18 (16%) of patients, negative in 92 (84%) of patients. cTnI was positive in 48 (44%) of patients, negative in 62 (56%) of patients. cTnT changed from negative to positive in 7 (6%) of patients, and from positive to negative in 8 (7%) of patients. After the follow-up, LVMI significantly increased in patients in which cTnT changed from negative to positive at follow-up. cTnI changed from negative to positive in 33 (30%) of patients, and from positive to negative in 12 (11%) of patients. In contrast to cTnT, LVMI did not increase in patients in which cTnI changed from negative to positive at fol-low-up. There were 5 patients in which both troponins negative in baseline and changed to positive at follow-up. LVMI was also significantly increased in these patients (149±40 kg/m 2 vs 194±42 kg/m 2 , p=0.043). Conclusions: Change of troponins from negative to positive over time may be a marker of the increase of LVMI in patients with ESRD.

European Journal of Echocardiography, 2003

Objective: To investigate the clinical value of quantitative assessment of myocardial perfusion(M... more Objective: To investigate the clinical value of quantitative assessment of myocardial perfusion(MP) for patients with coronary heart disease using global acoustic density technique(GAD) and real-time contrast echocardiography. Methods: Nineteen patients with coronary heart disease were performed contrast echocardiography using SonoVue (Bracco) intravenously. Four-chamber and twochamber view of left ventricular at apical were obtained. The MP were assessed quantitatively by GAD. Results: Quantitative methods using GAD: the MP were significantly higher in segments supplied by normal coronary arteries than those supplied by narrowed ones(22.09±18.12dB2/s vs 61.94±31.01 dB2/s, p<0.01). The MP were still lower in segments supplied by coronary arteries after PTCA and stenting than that by normal supply(28.84±23.94 dB2/s vs 66.12±33.46 dB2/s,p<0.01). However, the MP in segments supplied by coronary arteries after CABG were similar to that by normal supply (64.11±23.61dB2/s vs 61.94±31.01 dB2/s,p>0.05). Conclusions: Real-time contrast echocardiography and GAD can quantitatively evaluate the MP in patients with coronary heart disease.

Clinical science (London, England : 1979), 2004

In the present study, we sought to investigate the effects of differing inotropic conditions on r... more In the present study, we sought to investigate the effects of differing inotropic conditions on regional myocardial function in ischaemic segments. In an experimental pig model ( n =11), the regional deformation parameters peak systolic strain rate [SR(SYS) (peak velocity of thickening)], systolic strain [epsilon(SYS) (systolic wall thickening)] and post-systolic strain [epsilon(PST) (ongoing wall thickening after end of systole)] were measured during normal perfusion and regional ischaemia of the posterior wall. These parameters were compared with global contractility [E(ES) (end-systolic elastance)] measured by a conductance catheter. Ischaemia was induced by an active coronary hypoperfusion in the circumflex coronary artery. Measurements were done at baseline, during dobutamine and during esmolol infusion. In normal perfused hearts, SR(SYS) (4.8+/-0.2 s(-1) at baseline) increased during dobutamine infusion, decreased during esmolol infusion and correlated significantly with globa...

Circulation, Jan 16, 2003

Enzyme replacement therapy (ERT) has been shown to enhance microvascular endothelial globotriaosy... more Enzyme replacement therapy (ERT) has been shown to enhance microvascular endothelial globotriaosylceramide clearance in the hearts of patients with Fabry disease. Whether these results can be translated into an improvement of myocardial function has yet to be demonstrated. Sixteen patients with Fabry disease who were treated in an open-label study with 1.0 mg/kg body weight of recombinant alpha-Gal A (agalsidase beta, Fabrazyme) were followed up for 12 months. Myocardial function was quantified by ultrasonic strain rate imaging to assess radial and longitudinal myocardial deformation. End-diastolic thickness of the left ventricular posterior wall and myocardial mass (assessed by magnetic resonance imaging, n=10) was measured at baseline and after 12 months of ERT. Data were compared with 16 age-matched healthy controls. At baseline, both peak systolic strain rate and systolic strain were significantly reduced in the radial and longitudinal direction in patients compared with control...

European Journal of Medical Research, 2015

Right ventricle (RV) dysfunction is a key outcome determinant and a leading cause of death for pa... more Right ventricle (RV) dysfunction is a key outcome determinant and a leading cause of death for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we followed the 5-year clinical journey of a patient with CTEPH. The tricuspid pressure gradient was significantly increased in the early phase of CTEPH and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;normalized&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; at the late phase of this patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s clinical journey, but this &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;normalized&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; gradient is not a positive treatment response but rather an ominous sign of advancing right heart failure owing to an exhaustion of RV contractile function. Thus, appropriate interpretation of the tricuspid pressure gradient change is of importance for assessing RV dysfunction and treatment outcome during follow-up in patients with CTEPH. Besides systolic pulmonary artery pressure (SPAP), other RV functional parameters such as tricuspid annular plane systolic excursion, RV fractional area change, and RV longitudinal strain, together with clinical markers, may provide additional guidance regarding functional improvement or progression in patients with CTEPH.

Journal of the American Society of Echocardiography, 2002

We investigated the ability of ultrasonic strain rate (SR) and strain (epsilon) to quantify the c... more We investigated the ability of ultrasonic strain rate (SR) and strain (epsilon) to quantify the changes in normal myocardial function at varying inotropic states and heart rates (HR) in an attempt to determine whether these new regional function indices are potentially robust enough to quantitate stress echocardiography. Twenty closed-chest pigs underwent incremental atrial pacing (AP: 120-180/min, n = 7), dobutamine infusion (DI: 2.5-20 microg/kg/min, n = 7) or esmolol infusion with subsequent pacing (EI: 0.5 +/- 0.15 mg/kg/min with pacing 120-180/min, n = 6). Radial deformation of the left ventricular posterior wall was interrogated using the parasternal short-axis view to derive regional systolic SR and epsilon values. At baseline SR and epsilon averaged 5.0 +/- 0.4 s(-1) and 60% +/- 4%, respectively. SR remained unchanged during AP and increased linearly with DI (at 2.5 microg/kg/min = 6.2 +/- 0.3 s(-1), P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05 vs baseline; at 20 microg/kg/min = 9.9 +/- 0.7 s(-1), P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001 vs baseline), whereas EI resulted in a constant decrease of 30% +/- 4% in SR (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05). SR and left ventricular dP/dt(MAX) correlated linearly over the induced change in inotropic states and HR (r = 0.82; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). Conversely, epsilon values decreased during AP (at 180/min = 36% +/- 2%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). During DI, epsilon initially increased at 2.5 and 5 microg/kg/min (at 5 microg/kg/min = 77% +/- 6%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05) and decreased for higher doses because of increasing HR. EI resulted in a decrease of 30% +/- 4% in epsilon with a further decrease during subsequent pacing. epsilon correlated linearly with left ventricular ejection fraction (r = 0.87; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). Both SR and epsilon can quantify the changes in myocardial function during a range of inotropic challenges and over the range of physiologic HRs encountered during clinical stress echocardiography. SR may reflect regional contractile function, whereas epsilon reflects changes in ventricular geometry. This study would suggest that for quantitative stress echocardiography SR is better in quantification of changes in contractile function being relatively independent of HR.

Lecture Notes in Computer Science, 2001

Localized, regional ischaemia induces reduced systolic thickening with a concomi-tant increase in... more Localized, regional ischaemia induces reduced systolic thickening with a concomi-tant increase in post-systolic thickening (PST). Prior experimental and clinical observations proposed acute development and presence of PST in an ischaemic myocardial segment as a potential ...

Ultrasound in Medicine & Biology, 2009

Fabry disease is a rare X-linked lysosomal storage disorder leading to an accumulation of glycosp... more Fabry disease is a rare X-linked lysosomal storage disorder leading to an accumulation of glycosphingolipids in all tissues and organs including the heart. Among the pathologies of myocardial involvement, reviews and registry data list affection of heart valves and its hemodynamic significance as predominant alterations during progression of the disease. We thought to approach this uncertainty with a systematic observational study. In a single center study, 111 patients with genetically proven Fabry disease were systematically investigated by echocardiography for abnormalities of the valves in the left (aortic and mitral valve) and right heart (pulmonary and tricuspid valve). In addition, 60 patients were followed by echocardiography for 2.7 ؎ 1.5 y (range 1 to 6). Both valve stenosis and regurgitation were classified as mild, moderate or severe. Overall, no patient had severe heart valve abnormalities. The most frequent findings were mild aortic (n ‫؍‬ 17), mitral (n ‫؍‬ 57) and tricuspid (n ‫؍‬ 38) valve regurgitation. Only two patients showed mild aortic valve stenosis. Moderate aortic (n ‫؍‬ 1), mitral (n ‫؍‬ 2) or tricuspid (n ‫؍‬ 1) regurgitation were rarely detected. All Fabry patients in advanced stages (n ‫؍‬ 9) had only mild mitral regurgitation and one of them had mild aortic and mitral regurgitation, moderate tricuspid regurgitation and mild aortic stenosis. Thirty patients had completely normal valve function. There was no significant change toward hemodynamic relevant heart valve abnormalities during follow-up. Mild left ventricular valve regurgitations are frequent in Fabry disease. However, these valve abnormalities are not the major limitations for the Fabry heart. (E-mail: weidemann_f@medizin.uni-wuerzburg.de)

The assessment of left ventricular (LV) systolic function is often the most important information... more The assessment of left ventricular (LV) systolic function is often the most important information obtained during clinical echocardiography. Although LV systolic function may be visually estimated in many patients with or without contrast opacification, technically difficult patients may require alternative methods for evaluating LV systolic function. In this review, the authors describe several surrogate echocardiographic methods that might be helpful for the evaluation of LV systolic function in patients with poor image quality, including endocardial border delineation by contrast agents, mitral annular plane systolic excursion, mitral annular velocity derived from tissue Doppler, systolic time intervals, mitral regurgitation-derived LV dP/dt, and estimation of cardiac output by Doppler echocardiography. After a short introduction to the various issues involved, the authors propose a method for suitable measurement. In addition, indications and clinical implications, as well as limitations, of the different methods are discussed. (J Am Soc Echocardiogr 2013;26:105-13.)

Cardiac Function and Heart Failure (6.7% ) to infection. In 2 patients (13.3%) the cause of death... more Cardiac Function and Heart Failure (6.7% ) to infection. In 2 patients (13.3%) the cause of death was unknown. Of the 10 patients who died in connection with biopsy-proven AR, 6 also had relevant CAV that developed after the second post-HTx year. In 10 patients with moderate/severe late ARs, but without CAV during their first episode of late AR diagnosed at 4.6± 3.0 years after HTx, the angiogram showed relevant CAV lesions 2.4± 1.3 years after the first late AR. The mean number of late ARs/patient/year was higher in those with angiographic CAV that developed after the second post-HTx year than in those without CAV after >2 years since HTx (p<0.01). Conclusions: Late ARs are the major cause of late allograft dysfunction in children and may also be involved in the development of CAV. Together with CAV, late ARs are the dominant cause of death after the second post-HTx year and thus, continuous and close rejection surveillance late after HTx is justified to improve the long-term outcome.

Fabry disease is a rare X-linked storage disorder leading to an accumulation of globotriaosylcera... more Fabry disease is a rare X-linked storage disorder leading to an accumulation of globotriaosylceramides in all cells carrying lysosomes. As the accumulation occurs in most organs, different medical specialties are involved in the diagnostics and therapy of Fabry disease. With this review of the 3 main specialties (cardiology, nephrology, and neurology) and, in addition, the adjacent specialties (ophthalmology and dermatology), we aim to discuss the division-related responsibilities and want to suggest an organ-related additional therapy besides enzyme replacement therapy. Figure 5 (A) Angiomas/angiokeratomas on the skin of a Fabry patient "bathing trunk pattern." (B) Typical mucosal lesions.

DMW - Deutsche Medizinische Wochenschrift, 2008