The dorsal tangent line - A new approach in the radiological analysis of metacarpal fractures.

Traditionally, the angle between the intersecting central axes (lateral projection intersecting central axes - LCA) of the proximal and distal fragments of metacarpal fractures is measured on radiographs. We recommend using the angle between the intersecting dorsal tangent lines instead (lateral projection intersecting dorsal tangent lines - LDT). We analyzed radiographs of 25 fractures of the fifth metacarpal bone shaft in three planes. Intraclass correlation coefficients (ICC) were used to estimate inter-rater and intra-rater reliability. Mean palmar tilt was 35.6° ± 12.5° according to LCA and 27.6° ± 12.0° according to LDT. There were no differences during repeated measurements. Intra-rater reliability was high: ICC (95% CI) for LDT was 0.82 (0.74-0.88) and for LCA it was 0.71 (0.51-0.83). Mean values of palmar tilt using LCA exceeded those using LDT by 8.0° ± 7.7° (p < 0.001). Only LDT measurements provided comparable results between all raters. In conclusion, we demonstrated the feasibility and reliability of intersecting dorsal tangent lines for measuring palmar tilt in fifth metacarpal fractures as an alternative to the commonly used angle between the intersecting central axes.

Longer-term recurrence rate after low versus high dose radioiodine ablation for differentiated thyroid Cancer in low and intermediate risk patients: a meta-analysis.

BACKGROUND: Regarding the longer-term recurrence rate the optimal activity for the remnant thyroid ablation in patients with differentiated thyroid cancer (DTC) is discussed controversially. For the short-term ablation success rate up to 12 months there are already several meta-analyses. In this study we performed the first meta-analysis regarding the longer-term recurrence rate after radioactive 131-I administration. METHODS: We conducted an electronic search using PubMed/MEDLINE, EMBASE and the Cochrane Library. All randomized controlled trials (RCTs) assessed the recurrence rate after radioactive iodine ablation in patients with DTC, with a follow-up of at least two years were selected. Statistics were performed by using Review Manager version 5.3 and Stata software. RESULTS: Four RCTs were included in the study, involving 1501 patients. There was no indication for heterogeneity (I2 = 0%) and publication bias. The recurrence rate among patients who had a low dose 131-iodine ablation was not higher than for a high dose activity (odds ratio (OR) 0.93 [95% confidence interval (CI) 0.53-1.63]; P = 0.79). The mean follow-up time was between 4.25 and 10 years. The subgroup analysis regarding the TSH stimulated thyroglobulin values (< 10 ng/mL versus < 2 ng/mL versus ≤1 ng/mL) showed no influence on recurrence rate. CONCLUSIONS: For the first time we showed that the longer-term, at least 2-year follow-up, recurrence rate among patients who had 131-iodine ablation with 1.1 GBq was not higher than with 3.7 GBq.

Myocardial lipid content in Fabry disease: a combined 1H-MR spectroscopy and MR imaging study at 3 Tesla.

BACKGROUND: Fabry disease is characterized by a progressive deposition of sphingolipids in different organ systems, whereby cardiac involvement leads to death. We hypothesize that lysosomal storage of sphingolipids in the heart as occurring in Fabry disease does not reflect in higher cardiac lipid concentrations detectable by 1H magnetic resonance spectroscopy (MRS) at 3 Tesla. METHODS: Myocardial lipid content was quantified in vivo by 1H-MRS in 30 patients (12 male, 18 female; 18 patients treated with enzyme replacement therapy) with genetically proven Fabry disease and in 30 healthy controls. The study protocol combined 1H-MRS with cardiac cine imaging and LGE MRI in a single examination. RESULTS: Myocardial lipid content was not significantly elevated in Fabry disease (p = 0.225). Left ventricular (LV) mass was significantly higher in patients suffering from Fabry disease compared to controls (p = 0.019). Comparison of patients without signs of myocardial fibrosis in MRI (LGE negative; n = 12) to patients with signs of fibrosis (LGE positive; n = 18) revealed similar myocardial lipid content in both groups (p > 0.05), while the latter showed a trend towards elevated LV mass (p = 0.076). CONCLUSIONS: This study demonstrates the potential of lipid metabolic investigation embedded in a comprehensive examination of cardiac morphology and function in Fabry disease. There was no evidence that lysosomal storage of sphingolipids influences cardiac lipid content as measured by 1H-MRS. Finally, the authors share the opinion that a comprehensive cardiac examination including three subsections (LGE; 1H-MRS; T1 mapping), could hold the highest potential for the final assessment of early and late myocardial changes in Fabry disease.

[Assessment of systolic function in patients with poor echogenicity: echocardiographic methods]. / Abschätzung der linksventrikulären systolischen Funktion bei Patienten mit schlechter Bildqualität : Echokardiographische Methoden.

The visual echocardiographic evaluation of left ventricular (LV) systolic function can be cumbersome, especially in patients with poor image quality. This review describes several alternative echocardiographic methods to determine LV systolic function: endocardial border delineation by contrast agents, mitral annular plane systolic excursion, mitral annular velocity derived from tissue Doppler, myocardial performance index, mitral regurgitation derived LV dP/dtMax and estimation of cardiac output by Doppler echocardiography. The review introduces the respective methods along with the presentation of suitable measurements, clinical implications and methodological limitations.

[Heart involvement in Friedreich's ataxia]. / Herzbeteiligung bei Friedreich-Ataxie.

Friedreich's ataxia is a rare hereditary disease and although the gene defect has already been identified as a deficiency of the mitochondrial protein frataxin, the pathophysiology is still unknown. Although a multisystem disorder organ involvement is predominantly neurological. Besides the characteristic features of spinocerebellar ataxia the heart is frequently also affected. Cardiac involvement typically manifests as hypertrophic cardiomyopathy, which can progress to heart failure and death. So far most research has focused on the neurological aspects and cardiac involvement in Friedreich's ataxia has not been systematically investigated. Thus, a better understanding of the progression of the cardiomyopathy, cardiac complications and long-term cardiac outcome is warranted. Although no specific treatment is available general cardiac therapeutic options for cardiomyopathy should be considered. The current review focuses on clinical and diagnostic features of cardiomyopathy and discusses potential therapeutic developments for Friedreich's ataxia.

Uncertain diagnosis of Fabry disease: consensus recommendation on diagnosis in adults with left ventricular hypertrophy and genetic variants of unknown significance.

BACKGROUND: Screening in subjects with left ventricular hypertrophy (LVH) reveals a high prevalence of Fabry disease (FD). Often, a diagnosis is uncertain because characteristic clinical features are absent and genetic variants of unknown significance (GVUS) in the α-galactosidase A (GLA) gene are identified. This carries a risk of misdiagnosis, inappropriate counselling and extremely expensive treatment. We developed a diagnostic algorithm for adults with LVH (maximal wall thickness (MWT) of >12 mm), GLA GVUS and an uncertain diagnosis of FD. METHODS: A Delphi method was used to reach a consensus between FD experts. We performed a systematic review selecting criteria on electrocardiogram, MRI and echocardiography to confirm or exclude FD. Criteria for a definite or uncertain diagnosis and a gold standard were defined. RESULTS: A definite diagnosis of FD was defined as follows: a GLA mutation with ≤ 5% GLA activity (leucocytes, mean of reference value, males only) with ≥ 1 characteristic FD symptom or sign (neuropathic pain, cornea verticillata, angiokeratoma) or increased plasma (lyso)Gb3 (classical male range) or family members with definite FD. Subjects with LVH failing these criteria have a GVUS and an uncertain diagnosis. The gold standard was defined as characteristic storage in an endomyocardial biopsy on electron microscopy. Abnormally low voltages on ECG and severe LVH (MWT>15 mm) <20 years exclude FD. Other criteria were rejected due to insufficient evidence. CONCLUSIONS: In adults with unexplained LVH and a GLA GVUS, severe LVH at young age and low voltages on ECG exclude FD. If absent, an endomyocardial biopsy with electron microscopy should be performed.

Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications.

OBJECTIVE: The long-term effects of enzyme-replacement therapy (ERT) in Fabry disease are unknown. Thus, the aim of this study was to determine whether ERT in patients with advanced Fabry disease affects progression towards 'hard' clinical end-points in comparison with the natural course of the disease. METHODS: A total of 40 patients with genetically proven Fabry disease (mean age 40 ± 9 years; n = 9 women) were treated prospectively with ERT for 6 years. In addition, 40 subjects from the Fabry Registry, matched for age, sex, chronic kidney disease stage and previous transient ischaemic attack (TIA), served as a comparison group. The main outcome was a composite of stroke, end-stage renal disease (ESRD) and death. Secondary outcomes included changes in myocardial left ventricular (LV) wall thickness and replacement fibrosis, change in glomerular filtration rate (GFR), new TIA and change in neuropathic pain. RESULTS: During a median follow-up of 6.0 years (bottom and top quartiles: 5.1, 7.2), 15 events occurred in 13 patients (n = 7 deaths, n = 4 cases of ESRD and n = 4 strokes). Sudden death occurred (n = 6) only in patients with documented ventricular tachycardia and myocardial replacement fibrosis. The annual progression of myocardial LV fibrosis in the entire cohort was 0.6 ± 0.7%. As a result, posterior end-diastolic wall thinning was observed (baseline, 13.2 ± 2.0 mm; follow-up, 11.4 ± 2.1 mm; P < 0.01). GFR decreased by 2.3 ± 4.6 mL min(-1) per year. Three patients experienced a TIA. The major clinical symptom was neuropathic pain (n = 37), and this symptom improved in 25 patients. The event rate was not different between the ERT group and the untreated (natural history) group of the Fabry Registry. CONCLUSION: Despite ERT, clinically meaningful events including sudden cardiac death continue to develop in patients with advanced Fabry disease.

Recommendations on reintroduction of agalsidase Beta for patients with fabry disease in europe, following a period of shortage.

The interruption of the manufacturing process of agalsidase beta has led to a worldwide shortage of this drug. In the EU, nearly all patients initially reduced their agalsidase beta dose, and many of these switched to agalsidase alfa (Replagal Shire HGT). The clinical consequences of this period of drug shortage need to be further evaluated. A gradual increase of agalsidase beta supply is now expected. This implies that patients could resume or even commence agalsidase beta treatment. Guidance for prioritization of patients is needed to support equitable distribution of agalsidase beta to EU member states. To achieve this, in absence of level I clinical evidence, a draft consensus proposal was initiated and distributed. No full consensus was achieved, as there is disagreement regarding the indications for switching patients from agalsidase alfa to agalsidase beta. Some physicians support the concept that the 1.0 mg/kg EOW dose of agalsidase beta is more effective than agalsidase alfa at 0.2 mg/kg EOW, while others believe that at recommended dose, the preparations are equivalent. In light of these difficulties and the uncertainties with respect to supply of agalsidase beta, recommendations were agreed upon by a subgroup of physicians. These current recommendations focus on prioritization of criteria indicative of disease progression.

[Assessment of diastolic heart failure. Current role of echocardiography]. / Beurteilung der diastolischen Herzinsuffizienz. Aktueller Stellenwert der Echokardiographie.

Diastolic heart failure, also known as heart failure with preserved left ventricular ejection fraction (HF-pEF), is responsible for approximately 50 % of all heart failure cases. According to current guidelines the diagnosis HF-pEF requires three criteria: (1) signs or symptoms of heart failure, (2) presence of a normal left ventricular ejection fraction and (3) evidence of diastolic dysfunction. Echocardiography is the diagnostic modality of choice, especially after ruling out other causes of dyspnea, such as pulmonary diseases, heart rhythm disturbances and volume overload. Important echocardiographic parameters for the assessment of diastolic function are atrial dimensions, myocardial mass, mitral inflow pattern, pulmonary vein flow, propagation velocity of mitral inflow and the tissue Doppler of the mitral annulus. Nevertheless, a complete echocardiographic examination should be performed in every patient with heart failure. In general, diastolic dysfunction is frequently associated with increased atrial diameter and left ventricular hypertrophy. In advanced stages pulmonary hypertension can be present. A robust method for evaluation of systolic function in patients with diastolic dysfunction is crucial. The mitral inflow pattern provides various parameters to describe diastolic function (E/A ratio, deceleration time, isovolumetric relaxation time). In case of difficulties to separate a normal from a pseudonormal mitral inflow pattern the Valsalva maneuver can be used. Another valuable parameter for this differentiation is the duration of the backward flow in the pulmonary veins in contrast to forward flow over the mitral valve. Tachycardia or atrial fibrillation is a major problem for grading of diastolic function; however, in patients with atrial fibrillation E/e' is a well-established parameter. In summary, this review provides a detailed overview and discussion of the established and newer echocardiography techniques for the evaluation of diastolic function and provides an algorithm for the assessment of diastolic dysfunction in everyday routine.

[Low flow/low gradient aortic valve stenosis : clinical and diagnostic management]. / "Low-Flow/Low-Gradient"-Aortenklappenstenose : Klinisches und diagnostisches Spektrum.

Low gradient aortic stenoses (AS) represent a special challenge for physicians with respect to an exact diagnosis and optimal therapy. The difficulty lies in the estimation of the severity of AS which is decisive for subsequent treatment and the prognosis. Low flow and low gradient can be due to systolic or diastolic dysfunction by high-grade as well as by medium-grade AS and be of non-valvular origin. The latter group is to be interpreted as pseudoaortic stenosis as long as the low flow can successfully be raised by interventional means. However, only patients in the first group can be expected to profit from valve replacement and for patients in the second group the accompanying diseases must be the focus of therapeutic treatment. Therefore, according to recent European surveys up to 30% of patients with severe AS are undertreated due to false estimation of the severity of stenosis and perioperative risk stratification. Furthermore, follow-up investigations have shown that patients with low flow/low gradient stenosis and borderline-normal ejection fraction (EF) are in an advanced stage of the disease because they have often developed a severe reduction in longitudinal myocardial function and in addition have pronounced myocardial replacement fibrosis due to cardiac remodelling despite a preserved EF. Therefore, aortic valve area, mean pressure gradient and EF alone cannot be taken into consideration for the management of patients with severe AS but a comprehensive assessment of the hemodynamics, such as stroke volume, special functional parameters as well as individual clinical appearance is essential for precise diagnostic and therapeutic decision making.

[Echocardiography in diabetic cardiomyopathy]. / Echokardiographie bei diabetischer Kardiomyopathie.

The term diabetic cardiomyopathy was initially introduced in the 1980s when evidence was found that diabetes leads to a distinct cardiomyopathy, independent of coronary artery disease or hypertension. The detection of diabetic cardiomyopathy using echocardiography is challenging because no pathognomonic signs exist; however, it is the merit especially of the newer echocardiographic techniques, such as deformation imaging, that it is now possible to describe the morphology and function of diabetic hearts. Unfortunately, no long-term echocardiography studies are available describing disease progression in detail. Therefore, staging and differential diagnosis of diabetic cardiomyopathy remains challenging. This review tries to fill this gap by presenting a possible echocardiographic staging algorithm. Early stages of diabetic cardiomyopathy are marked by a deterioration of longitudinal systolic function and a compensative elevated radial function. Diastolic dysfunction is another early sign. When the disease progresses the functional deterioration is accompanied by morphological changes, such as left ventricular concentric hypertrophy and fibrosis. End stage disease is characterized by reduced ejection fraction and ventricular dilatation. Very late stage can mimic dilative cardiomyopathy.

[Pain therapy for Fabry's disease]. / Schmerztherapie bei Morbus Fabry.

Fabry's disease is an X-chromosome linked lysosomal storage disorder with α-galactosidase A deficiency and subsequent multiple organ involvement. An early and common symptom also in later stages of the disease is pain. This pain depends on various precipitating factors and can severely compromise the quality of life. So-called Fabry crises can lead to the necessity for intensive care treatment. The pain can be classified as predominantly neuropathic and is difficult to treat. In addition, medication has to be adjusted to concomitant cardiac and renal involvement in Fabry's disease. This review gives guidance for pain therapy in Fabry's disease based on the available evidence and on experience.

Non-invasive determination of myocardial lipid content in Fabry disease by 1H-MR spectroscopy.

PURPOSE: In Fabry disease (FD), a progressive deposition of sphingolipids is reported in different organs. The present study applied 1H magnetic resonance spectroscopy (MRS) to investigate the myocardial lipid content in FD. MATERIALS AND METHODS: In patients (PTS, n = 15) with genetically proven FD, 1H MRS of the heart was acquired in the same examination as routine cardiac cine and late enhancement MR imaging. Healthy volunteers (n = 11) without history of cardiac disease served as control (CTL). Myocardial triglycerides in vivo were quantified in 1H MRS. Left ventricular (LV) ejection fraction (EF) and late enhancement were assessed for the determination of LV systolic function, and onset or absence of myocardial fibrosis. RESULTS: All 1H MRS revealed resonances for intramyocardial triglycerides. Clinical parameters, e.g. EF (PTS 64 ± 2 % vs. CTL 61 ± 1 %) were similar in PTS and CTL or showed a non-significant trend (LV mass). Apart from a single patient with elevated myocardial triglycerides, no significant impact of Fabry disease on the triglyceride/water resonance ratio (PTS 0.47 ± 0.11 vs. CTL 0.52 ± 0.11 %) was observed in our patient cohort. CONCLUSION: A comprehensive cardiac evaluation of morphology, function as well as metabolism in Fabry PTS with suspected cardiac involvement is feasible in a single examination. No significant effect of myocardial triglyceride deposition could be observed in patients. The remarkably high myocardial triglyceride content in one patient with advanced FD warrants further studies in PTS with an extended history of the disease.

Right ventricular involvement in patients with Fabry's disease and the effect of enzyme replacement therapy.

PURPOSE: According to echocardiography reports, Fabry cardiomyopathy not only affects the left ventricle (LV) but also the right ventricle (RV). Until now no MRI studies about the effect of enzyme replacement therapy (ERT) on the RV are available. We evaluated the effect of ERT on the RV. MATERIALS AND METHODS: In this prospective trial 14 patients with genetically proven Fabry's disease were examined using a 1.5 T MR scanner before ERT and after 13 ± 1 months of ERT. All patients underwent cardiac MR imaging and the RV/LV cardiac morphology and function were analyzed. RESULTS: At baseline examination the values were as follows: RV mass 31 ± 6 g/m (2), end-diastolic volume (EDV) 88 ± 13 ml/m (2), end-systolic volume (ESV) 39 ± 9 ml/m (2), stroke volume (SV) 49 ± 7 ml/m (2) and ejection fraction (EF) 56 ± 5 %. The RV mass and EDV decreased significantly after 13 ± 1 months on ERT (mass 27 ± 7 g/m (2), p < 0.05, EDV 76 ± 24 ml/m (2), p < 0.05), with no significant change of ESV (33 ± 13 ml/m (2)), SV (43 ± 12 ml/m (2)) and EF (57 ± 7 %). The LV mass (102 ± 26 g/m (2) vs. 94 ± 27 g/m (2), p < 0.05), EDV (76 ± 13 ml/m (2) vs. 66 ± 22 ml/m (2), p < 0.05) and ESV (29 ± 9 ml/m (2) vs. 23 ± 9 ml/m (2), p < 0.05) decreased significantly while the EF (64 ± 7 % vs. 66 ± 5 %; p < 0.05) increased significantly. CONCLUSION: Besides the known beneficial effect on the LV, ERT improves RV mass and EDV.

[The various forms of left ventricular hypertrophy: diagnostic value of echocardiography]. / Verschiedene Formen der linksventrikulären Hypertrophie: Differenzialdiagnostischer Beitrag der Echokardiographie.

Left ventricular hypertrophy is a non-specific physiological or maladaptive cardiac response to a large array of stimuli mediated by exercise and numerous cardiac and systemic diseases. The precise characterization and quantification of left ventricular hypertrophy may allow a more timely diagnosis of the underlying condition. The clinical reference standard to assess left ventricular hypertrophy is echocardiography, but a comprehensive description of how to approach this frequent finding in clinical practice is lacking. The current review systematically describes the typical echocardiographic patterns of important types of cardiac hypertrophy using both established and advanced imaging modalities. In hypertrophic obstructive cardiomyopathy a markedly reduced regional systolic function is found in the prominent thickened septum, whereas in essential arterial hypertension a typical concentric left ventricular hypertrophy with a less prominent basal septal bulge is present. The echocardiographic characteristics of cardiac amyloidosis are ventricular hypertrophy with sparkling granular myocardial texture and a small epicardial effusion. In addition, the strain rate curve for longitudinal function shows a typically reduced function which reaches maximum already in early systole. The typical feature of Friedreich cardiomyopathy is concentric left ventricular hypertrophy and sparkling granular texture with preserved regional systolic function. In Fabry cardiomyopathy a prominent papillary muscle is presented and a typical strain rate curve can be extracted from the basal lateral wall, indicating replacement fibrosis. Prominent hypertrabecularisation (ratio of non-compacted to compacted myocardium >2) in the apical and mid left ventricular segments is typical for non-compaction cardiomyopathy. Knowledge of these typical echocardiographic features enables the cardiologist to distinguish between the different hypertrophic entities, thus paving the way to early diagnosis.

[Functional cardiac MRI for assessment of aortic valve disease]. / Aortenklappenstenose im MRT mit Dynamik und 3D.

Aortic valve disease shows a rising incidence with the increasing mean age of Western populations. The detection of hemodynamic parameters, which transcends the mere assessment of valve morphology, has an important future potential concerning classification of the severity of disease. MRI allows a non-invasive and a spatially flexible view of the aortic valve and the adjacent anatomic region, left ventricular outflow tract (LVOT) and ascending aorta. Moreover, the technique allows the determination of functional hemodynamic parameters, such as flow velocities and effective orifice areas. The new approach of a serial systolic planimetry velocity-encoded MRI sequence (VENC-MRI) facilitates the sizing of blood-filled cardiac structures with the registration of changes in magnitude during systole. Additionally, the subvalvular VENC-MRI measurements improve the clinically important exact determination of the LVOT area with respect to its specific eccentric configuration and its systolic deformity.

Cardiac challenges in patients with Fabry disease.

Fabry disease, an X-linked lysosomal storage disorder affecting both men and women, is a relatively prevalent cause of hypertrophic cardiomyopathy (HCM) and is associated with significant morbidity and early death due to heart failure or ventricular arrhythmias. Fabry cardiomyopathy results from progressive build-up of glycosphingolipids in cardiac structures, but the underlying complex pathophysiologic mechanisms remain poorly understood. Disease-specific enzyme replacement therapy (ERT) is available for Fabry disease and, therefore, attention should be focused on early diagnosis of this progressive, life-threatening disease. Selected cardiology patients at high risk for Fabry disease can be tested using simple enzymatic assays, and diagnosis is confirmed by demonstration of a Fabry mutation. Testing cardiology patients with HCM of unknown etiology may identify previously unrecognized Fabry patients and allow genetic mapping to be carried out to identify other affected family members at a relatively early stage of the disease. Timely intervention early on in the disease is a key, as the best responses to ERT are seen in patients with the lowest degree of cardiac hypertrophy and fibrosis at the start of treatment.