Early repolarisation

The electrocardiographic phenotype of early repolarisation, or “EARLY REPOLARISATION PATTERN” (ERP), has been known for decades and was generally considered a benign normal variant of the surface ECG. ERP is characterised by an arc or hook-shaped elevation at the QRS-ST junction, which leads to a positive deflection called a J-wave. For some time now, there has been increasing evidence that ERP may be associated with an increased cardiovascular risk, but especially a risk of life-threatening cardiac arrhythmias. The occurrence of malignant arrhythmias in the presence of ERP is called “EARLY REPOLARISATION SYNDROME” (ERS).

Within the framework of large-scale, international genome-wide association studies, we are currently analysing genes responsible for ERP in order to shed more light on the pathomechanism for the development of malignant cardiac arrhythmias. The key question, however, is why only a small fraction of people with ERP on the surface ECG develop life-threatening arrhythmias and what criteria could be used to better characterise and ultimately protect these sub-populations. To this end, we are investigating, among other things, morphological cardiac changes in individuals with ERP. Overall, our studies are helping to improve our understanding of the pathophysiology of ERP and to develop risk prediction models that will help us to protect people with ERP from sudden cardiac deathA type of death associated mainly with cardiac rhythm disorders. Causes: sudden onset of rapid heartbeat sequence, such as ventricular tachycardia, ventricular fibrillation, ventricular flutter, or more rarely severe slowing of the heartbeat sequence, but also vascular occlusion, myocardial rupture or total AV block..

Publications

Teumer A*, Trenkwalder T*, Kessler T, Jamshidi Y, van den Berg ME, Kaess B, Nelson CP, Bastiaenen R, De Bortoli M, Rossini A, Deisenhofer I, Stark K, Assa S, Braund PS, Cabrera C, Dominiczak AF, Gögele M, Hall LM, Ikram MA, Kavousi M, Lackner KJ, Müller C, Münzel T, Nauck M, Padmanabhan S, Pfeiffer N, Spector TD, Uitterlinden AG, Verweij N, Völker U, Warren HR, Zafar M, Felix SB, Kors JA, Snieder H, Munroe PB, Pattaro C, Fuchsberger C, Schmidt G, Nolte IM, Schunkert H, Pramstaller P, Wild PS, van der Harst P, Stricker BH, Schnabel RB, Samani NJ, Hengstenberg C, Dörr M, Behr ER, Reinhard W. KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern. JCI Insight. 2019 Oct 10. pii: 131156.

Trenkwalder T, Rübsamen N, Schmitt VH, Arnold N, Kaess BM, Sinning CR, Zeller T, Beutel ME, Schmidtmann I, Nickels S, Pfeiffer N, Leuschner A, Münzel T, Lackner KJ, Hengstenberg C, Blankenberg S, Wild PS, Reinhard W, Schnabel R. Left ventricularArising from the ventricle. geometry and function in early repolarization: results from the population-based Gutenberg Health Study. Clin Res Cardiol. 2019 Feb 28.

Reinhard W, Trenkwalder T, Haller B, Meindl C, Schoenfeld J, Kaess BM, Hengstenberg C, Schunkert H, Pressler A, Hall M, Scherr J. The early repolarization pattern: Echocardiographic characteristics in elite athletes. Ann Noninvasive Electrocardiol. 2019 Mar;24(2):e12617.

Trenkwalder T, King R, Kaess BM, Hengstenberg C, Schunkert H, Ittermann T, Felix SB, Busch M, Dörr M, Reinhard W. Ventricular and Supraventricular Ectopy in Subjects With Early Repolarization. Am J Cardiol. 2017 Jul 1;120(1):92-97.

Reinhard W, Kaess BM, Debiec R, Nelson CP, Stark K, Tobin MD, Macfarlane PW, Tomaszewski M, Samani NJ, Hengstenberg C. Heritability of early repolarization: a population-based studyCirc Cardiovasc Genet. 2011 Apr;4(2):134-8. doi: 10.1161/CIRCGENETICS.110.958298. Epub 2011 Jan 31. 

Iron deficiency in heart failure

Up to 50 per cent of all patients with chronic heart failure have an iron deficiency. This is associated with reduced physical performance, impaired quality of life and increased mortality. These patients show improved performance and quality of life after intravenous(abbr. i.v.) into a vein, e.g. injection, infusion. compensation of iron deficiency. We are currently comparing different laboratory parameters for the diagnosis and treatment of clinically relevant iron deficiency. Since heart failure patients have chronic inflammation, we are particularly interested in inflammation-independent parameters such as soluble transferrin receptor (sTfR).

The aim of our work is a comparative clinical characterisation of patients with heart failure and iron deficiency according to the definition currently recommended in the ESC guidelines, as well as iron deficiency according to the definition of the Thomas plot, in order to find out which patients particularly benefit from iron supplementation.

Cardiac amyloidoses

Amyloidoses with cardiac involvement include light chain (AL) amyloidosis, transthyretin (ATTR) amyloidosis and rare forms such as AA amyloidosis. ATTR amyloidosis can be further divided into hereditary (m-) ATTR amyloidosis and age-related wild-type (wt-) ATTR amyloidosis. AL amyloidosis is considered the most common form, although wt-ATTR amyloidosis has been increasingly diagnosed since the development of specific scintigraphic techniques. The exact prevalence of wt-ATTR amyloidosis is still unknown, but it is assumed that the number of unreported cases is high. By means of echocardiographic, spiroergometric as well as molecular genetic analyses, we are working on the identification of diagnostic and prognostic parameters of ATTR amyloidosis.

Rare variants and rare diseases

Hereditary factors play a varying role in the occurrence and manifestation of various cardiovascular diseases. Genetic diagnostics has become increasingly important in the age of Next Generation Sequencing (NGS). NGS generates large amounts of data, which can only remain focused on the clinical question with the help of interpretation software and selected gene panels.

In addition to clear pathogenic mutations, however, so-called variants of unclear clinical significance (VUS) often appear, whose significance for a disease has not yet been clearly explained. The interpretation of such sequence deviations often presents the treating physicians with a clinical challenge.

One way of approaching these VUS is a structured segregation analysis of the family. The inheritance pattern of these rare genetic alterations as well as the phenotypic expression within a family can then provide important insights for future genetic diagnostics, but also for the pathophysiological understanding of these mostly rare diseases.

Publications

Trenkwalder T, Schunkert H, Reinhard W. Meaningful diagnostics: genetics. Herz. 2020 Feb;45(1):3-9.

Trenkwalder T, Schunkert H, Reinhard W. Cardiac involvement in storage diseases : Role of genetic diagnostics. Herz. 2019 Jun 24. Review. German.

Reinhard W, Trenkwalder T, Schunkert H. Practical guidelines for genetic testing in cardiovascular diseases. Herz. 2017 Aug;42(5):485-491. Review. German.

Trenkwalder T, Deisenhofer I, Hadamitzky M, Schunkert H, Reinhard W. Novel frame-shift mutation in PKP2 associated with arrhythmogenic right ventricular cardiomyopathyGeneric term for various, often genetically determined diseases of the heart muscle that are not the result of other diseases (heart valve defects, inflammations). The causes of this are often unknown. The heart may be significantly enlarged and its pumping power greatly reduced.: a case report. BMC Med Genet. 2015 Dec 23;16:117.

Telemedical care for heart failure patients

Our health system is facing the challenge of an increasingly ageing population, combined with an accumulation of chronic diseases. The result is new demands on the content of medical care, rising costs and a shortage of resources.

We are currently working in cooperation with Health Care Systems GmbH on improved outpatient care for patients with severe heart failure with the help of telemedical monitoring via a novel voice-controlled app. On the basis of automatically recorded daily voice inputs (voice interfaces) on the symptoms, as well as clinical parameters transmitted via Bluetooth, the situation-related need for action for the patient is analysed daily by means of artificial intelligence. If predefined alarms are triggered by a clinical deterioration of the patient, a medical diagnosis and, if necessary, an interventionA quick medical measure to slow down the progression of a disease, e.g. with the help of the cardiac catheter (interventional cardiac catheter technique) an acutely occluded coronary vessel is reopened and thus the spread of the heart attack area is stopped. in the sense of an adjustment of the therapy is carried out via the German Heart Centre Munich. In addition, the HCSG telemedical service centre takes over regular knowledge transfer adapted to the patient’s psychosocial environment on lifestyle in chronic heart failure.

In addition to the usability and acceptance of the novel, flexible voice-controlled program, we are investigating the telemedical monitoring of heart failure patients with regard to quality of life and functional parameters. The aim is to improve health care and use resources more efficiently.