[Atypical distal tibial shaft fractures in a patient with bilateral TKA and antiresorptive treatment]. / Atypische distale Tibiaschaftfrakturen bei liegenden KTEP beidseits unter antiresorptiver Therapie.

There are many cases in the literature that describe atypical femur fractures under antiresorptive therapy. Other localizations of fractures of this genesis, especially if occurring bilaterally, are rare. This case reports about the diagnosis, treatment and process of a 76-year old patient, who within a 4­month period suffered from bilateral distal tibial shaft fractures, after years of treatment with bisphosphonates, strontium ranelate and denosumab.

CMR-derived TAPSE measurement: a semi-quantitative method of right ventricular function assessment in patients with hypertrophic cardiomyopathy.

AIM: To compare cardiovascular magnetic resonance (CMR)-derived right ventricular fractional shortening (RVFS), tricuspid annular plane systolic excursion with a reference point within the right ventricular apex (TAPSEin) and with one outside the ventricle (TAPSEout) with the standard volumetric approach in patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: 105 patients with HCM and 20 healthy subjects underwent CMR. In patients with HCM, TAPSEin (r = 0.31, p = 0.001) and RVFS (r = 0.35, p = 0.0002) revealed a significant but weak correlation with right ventricular ejection fraction (RVEF), whereas TAPSEout (r = 0.57, p < 0.0001) showed a moderate correlation with RVEF. The ability to predict RVEF < 45 % in HCM patients was best for TAPSEout. In patients with hypertrophic obstructive cardiomyopathy (HOCM), RVEF showed a significant but weak correlation with TAPSEout (r = 0.36, p = 0.02) and no correlation with TAPSEin (r = 0.05, p = 0.07) and RVFS (r = 0.02, p = 0.2). In patients with hypertrophic non-obstructive cardiomyopathy (HNCM), there was a moderate correlation between RVEF and TAPSEout (r = 0.57, p < 0.0001) and a weak correlation with TAPSEin (r = 0.39, p = 0.001) and RVFS (r = 0.38, p = 0.002). In the 20 healthy controls, there was a strong correlation between RVEF and all semi-quantitative measurements. CONCLUSION: CMR-derived TAPSEin is not suitable to determine right ventricular function in HCM patients. TAPSEout showed a good correlation with RVEF in HNCM patients but only a weak correlation in HOCM patients. TAPSEout might be used for screening but the detection of subtle changes in RV function requires the 3D volumetric approach.

[Short QT syndrome]. / Short-QT-Syndrom.

Short QT syndrome was first described in 2000. It is a sporadic or familial ion channel disease that is associated with abbreviation of the QT interval permanently or transiently. The time of first manifestation of symptoms such as atrial fibrillation or syncope or even sudden death is between the 2nd and 4th decade. Sudden death has also been described for newborns and adolescents. Therapy depends on the severity of the symptoms. The therapy of choice for secondary prevention of sudden death is the implantable cardioverter-defibrillator (ICD). Quinidine has been shown to be effective in preventing arrhythmias in a number of patients. It is mostly used as an adjunct to the ICD but has also been used with considerable success in children and individuals who refused ICD implantation.

Insights into the location of type I ECG in patients with Brugada syndrome: correlation of ECG and cardiovascular magnetic resonance imaging.

BACKGROUND: Brugada syndrome is characterized by ST-segment abnormalities in V1-V3. Electrocardiogram (ECG) leads placed in the 3rd and 2nd intercostal spaces (ICSs) increased the sensitivity for the detection of a type I ECG pattern. The anatomic explanation for this finding is pending. OBJECTIVE: The purpose of the study was to correlate the location of the Brugada type I ECG with the anatomic location of the right ventricular outflow tract (RVOT). METHODS: Twenty patients with positive ajmaline challenge and 10 patients with spontaneous Brugada type I ECG performed by using 12 right precordial leads underwent cardiovascular magnetic resonance imaging (CMRI). The craniocaudal and lateral extent of the RVOT and maximal RVOT area were determined. Type I ECG pattern and maximal ST-segment elevation were correlated to extent and maximal RVOT area, respectively. RESULTS: In all patients, Brugada type I pattern was found in the 3rd ICS in sternal and left-parasternal positions. RVOT extent determined by using CMRI included the 3rd ICS in all patients. Maximal RVOT area was found in 3 patients in the 2nd ICS, in 5 patients in the 4th ICS, and in 22 patients in the 3rd ICS. CMRI predicted type I pattern with a sensitivity of 97.2%, specificity of 91.7%, positive predictive value of 88.6%, and negative predictive value of 98.0%. Maximal RVOT area coincided with maximal ST-segment elevation in 29 of 30 patients. CONCLUSION: RVOT localization determined by using CMRI correlates highly with the type I Brugada pattern. Lead positioning according to RVOT location improves the diagnosis of Brugada syndrome.

[Orthostatic hypotension : diagnosis and therapy]. / Orthostatische Hypotension : Diagnostik und Therapie.

Syncope is a frequent clinical event in the general population and occurs in up to every second patient during their lifetime. Reflex syncope is the most prevalent mechanism and is often triggered by orthostatic stress. Orthostatic hypotension (OH) represents a rare cause in young patients but is an important differential diagnosis in the aged. The Framingham study revealed an increase in the incidence of OH-triggered syncope from 5.7 events/1000 person-years at the age of 60-69 to 11.1 in men who are 70-79 years of age. OH often constitutes a chronic, debilitating illness with significant reduction in the quality of life. Important causes are volume loss, side effects of different vasoactive drugs, and neurodegenerative or secondary autonomic diseases following long-standing diabetes or amyloid disease. OH is difficult to treat. The therapeutic goal is to improve postural symptoms, standing time, and prevention of syncopal events. Drug therapy alone is never adequate. Because orthostatic stress varies during the day, a patient-tailored approach that emphasizes education and several general actions is recommended together with physical therapy and isometric exercise maneuvers. Moderate and severe cases require additional drug treatment to increase peripheral vascular resistance.

Arrhythmogenic hereditary syndromes: Brugada Syndrome, long QT syndrome, short QT syndrome and CPVT.

In approximately 10-20% of all sudden deaths no structural cardiac abnormalities can be identified. Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome and catecholaminergic polymorphic ventricular tachyarrhythmias. Each of these cardiac channelopathies is charaterized by unique genetic and clinical features. The resting ECG and the ECG under exercise are pivotal for the diagnosis of ion channel diseases. Molecular genetic screening can reveal underlying mutations in a variable degree among the cardiac ion channel diseases in up to 70% (LQTS) and may identify individuals with incomplete penetration of the disease. In patients with primary electrical diseases specific clinical triggers for arrhythmic events such as syncope or sudden cardiac death have been identified including exercise, strenuous activity, auditory stimuli or increased vagal tone. The significance of programmed ventricular stimulation is at present unclear concerning risk stratification in patients with Brugada syndrome and short QT syndrome and of no significance in long QT syndrome and catecholaminergic polymorphic ventricular tachycardias. The success of medical therapy remains modest for prevention of sudden cardiac death and may necessitate the insertion of an implantable cardioverter. However, side effects with inappropriate therapies in this patient group with often young and active individuals have to be encountered. More insights into the arrhythmogenesis is critical for future development of effective medical treatment strategies.

Evaluation and management of syncope.

Syncope is a common symptom and accounts for approximately 1% of all emergency visits. There are four main causes of syncope: reflex, neurally mediated syncope, orthostatic hypotension and cardiac syncope. The prognosis of patients with reflex syncopes is good, whereas patients with cardiac syncope are at increased risk for sudden cardiac death. The first diagnosic step after transient loss of consciousness the diagnosis syncope has to be established. It has to be differentiated from other forms of loss of consciousness according to current definition. Careful evaluation of the patient with syncope is mandatory. If the underlying cause of syncope can be diagnosed during initial evaluation, the patient should be treated accordingly. If the cause of syncope remains unclear, the patient has to be stratified with respect to the risk of a cardiovascular event and sudden cardiac death and further evaluation initiated. This review gives a comprehensive summary of definition, work-up and treatment of syncope based on the current guidelines for the evaluation of syncope.

[Magnetic navigation in invasive electrophysiological diagnostic and therapy]. / Magnetische Navigation in der elektrophysiologischen Diagnostik und Therapie.

Electrophysiological stimulation and ablation is currently performed with manually deflectable catheters of different lengths and curves. Disadvantages of conventional therapy are catheter stiffness, limited local stability, risk of dislocation or perforation, and reduced tissue contact in regions with difficult access. Fluoroscopy to control catheter movement and position may require substantial radiation times. Magnetic navigation was first applied for right heart catherization in congenital heart disease in 1991; the first electrophysiological application took place in 2003. Today, an ablation electrode with small magnets is aligned in the patient's heart by two external magnets positioned at both sides of the thorax. Antegrade and retrograde movement of the distal catheter tip are performed via an external device on the patient's thigh. Three-dimensional MRI scans acquired before intervention can be merged with electroanatomical reconstruction, leading to further reductions of radiation burden. During treatment of supraventricular tachyarrhythmias high local precision of magnetically guided catheters, good local stability, and a substantially reduced radiation time have been reported. First applications in ventricular tachyarrhythmias and complex congenital cardiac defects indicate a comparable effect. Limitations of this therapy are the application in left atrial procedures (open irrigated ablation catheters not yet available), difficult transaortic retrograde approach (high lead flexibility), and the considerable costs. Magnet-assisted navigation is feasible during percutaneous coronary interventions of tortuous coronary arteries and in positioning guidewires in coronary sinus side branches for resynchronisation therapy. Future applications will be complex left atrial procedures, magnetically guided cardiac stem cell therapy, local drug application, and extracardiac vessel therapy.

[Primary electrical heart disease in adulthood--electrophysiological findings and therapy]. / Primär elektrische Herzerkrankungen im Erwachsenenalter--Elektrophysiologische Befunde und Therapie.

Sudden cardiac death accounts for 100,000 victims in Germany per year. Predominantly, patients with structural heart disease such as coronary artery disease or dilated cardiomyopathy are affected. However, approximately 5-10% of sudden deaths hit patients without structural disease of the heart. The proportion of young patients (< 40 years of age) in this group is even higher (10-20%). In younger patients significantly more diseases like hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia and primary electrical diseases of the heart could be observed such as long QT syndrome, short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. The primary electrical diseases are different concerning their electrocardiographical pattern, clinical triggers of arrhythmias, results of invasive diagnostics and therapy. Meanwhile, molecular genetic screening can reveal specific mutations of ion channels and can identify consecutive functional defects. The significance of programmed ventricular stimulation is at present unclear concerning risk stratification in patients with Brugada syndrome and short QT syndrome and of no significance in long QT syndrome and catecholaminergic polymorphic ventricular tachycardias. The implantable cardioverter defibrillator is the therapy of choice in most symptomatic patients. With increasing knowledge as a result of sophisticated molecular genetic screening, identification of underlying ion channel defects and new details of the mechanisms of arrhythmogenesis, a potential genotype-guided therapy will gain more importance in the future.

[Magnetic resonance imaging of the brain in patients with cardiac pacemakers. Experimental and clinical investigations at 1.5 Tesla]. / MRT-Untersuchungen des Hirns bei Patienten mit implantierten Herzschrittmachern. Experimentelle und klinische Untersuchungen an einem 1.5 Tesla-System.

PURPOSE: In-vitro and In-vivo evaluation of feasibility and safety of MRI of the brain at 1.5 T in patients with implanted pacemakers (PM). MATERIALS AND METHODS: 24 PM models and 45 PM electrodes were tested In-vitro with respect to translational forces, heating of PM leads, behaviour of reed switch (activated vs. deactivated) and function at a 1.5 T MRI-system (actively shielded, maximum field gradient: 30 mT/m; rise time: 150 T/m/s). Based on these results, 63 MRI examinations in 45 patients with implanted PM were performed. Prior to MRI the PM were re-programmed in an asynchronous mode. The maximum SAR of MRI-sequences was limited to 1.2 W/kg. Continuous monitoring of ECG and pulse oximetry was performed during MRI. PM inquiry was performed prior to MRI, immediately after MRI and -- to assess long-term damages -- three months after the MRI exams, including determination of stimulation thresholds to assess potential thermal myocardial injuries at the lead tips. RESULTS: Translational forces (F (max) < or = 560 mN) and temperature increase (DeltaT (max) < or = 2.98 degrees C) were in a range which does not represent a safety concern from a biophysical point of view. No changes to the programmed parameters of the PM or damage of PM components were observed neither In-vitro (n = 0/24) nor In-vivo (n = 0/63). Despite the strong magnetic field, the reed switch remained deactivated in 54 % (13/24) of the cases during In-vitro simulated MRI exams of the brain. All patient studies (n = 63/63) could be completed without any complications. Atrial and ventricular stimulation thresholds (expressed as pulse duration at 2-fold rheobase) did not change significantly immediately post-MRI nor in the 3 months follow-up (pre-MRI: 0.17 ms +/- 0.13 ms, post-MRI: 0.18 ms +/- 0.14 ms, 3 months follow-up: 0.17 ms +/- 0.12 ms). CONCLUSION: MRI of the brain at 1.5 Tesla can be safely performed in carefully selected clinical circumstances when appropriate strategies are used (re-programming the PM to an asynchronous mode, continuous monitoring of ECG and pulse oximetry, limiting the SAR value of the MRI sequences, cardiological stand-by). Based on these studies, implanted PM should not longer be regarded as an absolute contraindication for MRI at 1.5 T.

Incidence and electrophysiological characteristics of spontaneous ventricular tachyarrhythmias in high risk coronary patients and prophylactic implantation of a defibrillator.

OBJECTIVES: To assess the incidence and electrophysiological characteristics of spontaneous ventricular tachyarrhythmias after implantable cardioverter-defibrillator (ICD) implantation for primary prevention. DESIGN: Prospective observational study. PATIENTS: 41 consecutive patients, who fulfilled MADIT (multicenter automatic defibrillator implantation trial) I criteria, except for suppressibility by procainamide, and who received a prophylactic ICD. INTERVENTIONS: Subpectoral implantation of an ICD. MAIN OUTCOME MEASURES: Incidence of ventricular tachyarrhythmias and their electrophysiological characteristics with respect to timing of the arrhythmia, tachyarrhythmia cycle length, mode of termination, and clinical relevance. RESULTS: During a mean (SD) follow up of 30 (21) months 18 of 41 (43.9%) patients experienced 142 appropriate ICD treatments. The mean (SD) time to first event was 9.6 (15.1) months. One patient had ventricular fibrillation (VF), 12 patients ventricular tachycardia (VT), and five both VT and VF. The mean (SD) cycle length of monomorphic VT was 306 (42) ms. Of 142 episodes, 117 (82.3%) were terminated by antitachycardia pacing and another 25 (17.6%) by ICD discharges. Cumulative survival of hypothetical death, defined as treated VT with a cycle length < 260 ms or VF, was 83.2% after one year and 78.4% after two years. CONCLUSIONS: Patients with a left ventricular ejection fraction < 35%, a history of myocardial infarction, non-sustained VT, and inducible VT/VF are at high risk of VT/VF early after implantation. Therefore, implantation of a tiered treatment defibrillator seems to be justified.

Amiodarone-associated "torsade de pointes". Relevance of concomitant cardiovascular medication in a patient with atrial fibrillation and structural heart disease.

A 69 year old female with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation suffered from occipital apoplexy. Under treatment with amiodarone 600 mg daily and concomitant medication with beta-acetyldigoxine (0.1 mg daily) and bisoprolole (1.25 mg daily), significant QT-prolongation (max. 700 ms; QTc: 614 ms) could be documented. Out of normofrequent sinus rhythm but as well out of bradycardia, the patient developed repetitive short-lasting "torsade de pointes" tachycardias (320 bpm) which terminated spontaneously. Serum electrolytes, plasma levels of digoxine (1.76 ng/ml) and amiodarone (1.9 mcg/ml) were within therapeutic range. This case report is the first to describe induction of amiodarone-associated "torsade de pointes" tachycardia during concomitant beta-blocker and digitalis medication in a patient with atrial fibrillation and structural heart disease. This points towards an elevated risk for proarrhythmia under this triple therapy.

TYRP1 is associated with dun coat colour in Dexter cattle or how now brown cow?

Tyrosinase related protein 1 (TYRP1), which is involved in the coat colour pathway, was mapped to BTA8 between microsatellites BL1080 and BM4006, using a microsatellite in intron 5 of TYRP1. The complete coding sequence of bovine TYRP1 was determined from cDNA derived from skin biopsies of cattle with various colours. Sequence data from exons 2-8 from cattle with diluted phenotypes was compared with that from non-diluted phenotypes. In addition, full-sib families of beef cattle generated by embryo transfer and half-sib families from traditional matings in which coat colour was segregating were used to correlate TYRP1 sequence variants with dilute coat colours. Two non-conservative amino acid changes were detected in Simmental, Charolais and Galloway cattle but these polymorphisms were not associated with diluted shades of black or red, nor with the dun coat colour of Galloway cattle or the taupe brown colour of Braunvieh and Brown Swiss cattle. However, in Dexter cattle all 25 cattle with a dun brown coat colour were homozygous for a H424Y change. One Dexter that was also homozygous Y434 was red because of an "E+/E+" genotype at MC1R which lead to the production of only phaeomelanin. None of the 70 remaining black or red Dexter cattle were homozygous for Y434. This tyrosine mutation was not found in any of the 121 cattle of other breeds that were examined.

Potential device interaction of a dual chamber implantable cardioverter defibrillator in a patient with continuous spinal cord stimulation.

Spinal cord or thalamic deep brain stimulation with a pacemaker is becoming more important in the treatment of drug refractory pain due to peripheral vascular disease, angina pectoris and intractable tremor in patients with neurologic disorders such as Parkinson's disease. An additional indication for a cardiac pacemaker or implantable cardioverter defibrillator raises concerns about possible interactions between the implanted electrical devices. We report on a patient with existing spinal cord stimulation who survived sudden cardiac death and received a dual chamber cardioverter defibrillator capable of delivering tiered therapies in both the atrium and ventricle.