Electromechanical vortex filaments during cardiac fibrillation.

The self-organized dynamics of vortex-like rotating waves, which are also known as scroll waves, are the basis of the formation of complex spatiotemporal patterns in many excitable chemical and biological systems. In the heart, filament-like phase singularities that are associated with three-dimensional scroll waves are considered to be the organizing centres of life-threatening cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and control of electromechanical turbulence in the heart are inherently three-dimensional phenomena. However, it has not previously been possible to visualize the three-dimensional spatiotemporal dynamics of scroll waves inside cardiac tissues. Here we show that three-dimensional mechanical scroll waves and filament-like phase singularities can be observed deep inside the contracting heart wall using high-resolution four-dimensional ultrasound-based strain imaging. We found that mechanical phase singularities co-exist with electrical phase singularities during cardiac fibrillation. We investigated the dynamics of electrical and mechanical phase singularities by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart. We show that cardiac fibrillation can be characterized using the three-dimensional spatiotemporal dynamics of mechanical phase singularities, which arise inside the fibrillating contracting ventricular wall. We demonstrate that electrical and mechanical phase singularities show complex interactions and we characterize their dynamics in terms of trajectories, topological charge and lifetime. We anticipate that our findings will provide novel perspectives for non-invasive diagnostic imaging and therapeutic applications.

[Less is more in cardiology and angiology]. / Weniger ist mehr in Kardiologie und Angiologie.

Cardiovascular medicine is one of the most resource-consuming parts of the healthcare system and many examples of overdiagnostic and overtreatment can be found. The present article presents just three of these, one from cardiology and two from vascular medicine. The topic of chronic coronary heart disease concerns the unequivocal proof of ischemia before a coronary intervention. The sections on Duplex sonography of the cervical blood vessels and the diagnostics of thrombophilia describe which valid clinical problems may justify the performance of these examinations at all. The potential for harm caused by overdiagnostics in both cases lies not only in the unnecessary use of resources but, more importantly, in the subsequent overtreatment. The few appropriate indications are described in detail.

Atrial fibrillation is frequent but does not affect risk stratification in pulmonary embolism.

BACKGROUND: Although prior studies indicate a high prevalence of atrial fibrillation (AF) in patients with pulmonary embolism (PE), the exact prevalence and prognostic impact are unknown. METHODS: We aimed to investigate the prevalence, risk factors and prognostic impact of AF on risk stratification, in-hospital adverse outcomes and mortality in 528 consecutive PE patients enrolled in a single-centre registry between 09/2008 and 09/2017. RESULTS: Overall, 52 patients (9.8%) had known AF and 57 (10.8%) presented with AF on admission; of those, 34 (59.6%) were newly diagnosed with AF. Compared to patients with no AF, overt hyperthyroidism was associated with newly diagnosed AF (OR 7.89 [2.99-20.86]), whilst cardiovascular risk comorbidities were more frequently observed in patients with known AF. Patients with AF on admission had more comorbidities, presented more frequently with tachycardia and elevated cardiac biomarkers and were hence stratified to higher risk classes. However, AF on admission had no impact on in-hospital adverse outcome (8.3%) and in-hospital mortality (4.5%). In multivariate logistic regression analyses corrected for AF on admission, NT-proBNP and troponin elevation as well as higher risk classes in risk assessment models remained independent predictors of an in-hospital adverse outcome. CONCLUSION: Atrial fibrillation is a frequent finding in PE, affecting more than 10% of patients. However, AF was not associated with a higher risk of in-hospital adverse outcomes and did not affect the prognostic performance of risk assessment strategies. Thus, our data support the use of risk stratification tools for patients with acute PE irrespective of the heart rhythm on admission.

[Apps in General Medicine : A topic for medical education?​]. / Apps in der Inneren Medizin : Ein Thema für das Medizinstudium?

BACKGROUND: Health-related apps can provide helpful resources for both doctors and patients. The selection of potentially useful apps and the appraisal of their quality are particularly important in the context of medicine as false or confusing app content may put patients at risk. AIM: In this article a brief overview of the topic is provided and the results of a pilot study, in which medical students tested and evaluated the quality of 143 health-related apps on the topics of cardiology and pulmonology are presented. MATERIAL AND METHODS: Using the semiautomated retrospective app store analysis (SARASA) method, a group of apps concerned with cardiology and pulmonology were identified from a pool of over 2,000,000 apps available in the Apple Store. As part of a practical exercise, 138 4th year medical students tested a total of 143 of these apps, subsequently evaluating them using a specially devised questionnaire. RESULTS: The most frequent target population among the tested apps was identified as patients and their carers and the primary purpose in the majority of cases was the provision of information. Despite this, at least one quarter of all apps tested required users to enter sensitive health-related information. The evaluations by the students portrayed a large range in terms of the quality of the apps tested. DISCUSSION: Health-related apps play a growing role in the management of illnesses in the field of internal medicine. Doctors must be aware of the benefits and limitations of using such apps and should be prepared during their medical studies for the challenge of advising patients on this topic.

[InterAtrial Shunt Device in diastolic heart failure]. / InterAtrial Shunt Device bei diastolischer Herzinsuffizienz.

All types of heart failure are associated with reduced cardiac output and/or increased left atrial (LA) pressure. In diastolic heart failure (heart failure with preserved ejection fraction [HFpEF]), the increased LA pressure plays a central role, leading to pulmonary venous hypertension (PVH) and increased pulmonary artery pressure. These pressure parameters are presumably decisive for the symptoms and mortally of heart failure, particularly of the diastolic form. This is the basis for treatment with an interarterial shunt to reduce LA pressure in patients with diastolic heart failure and PVH. At first glance, this appears paradoxical, since closure of an atrial septum defect serves to prevent increased pulmonary vascular resistance and paradoxical embolism. Prevention of increased pulmonary vascular resistance and paradoxical embolism is thus an essential aspect in the development of devices for establishing an interarterial shunt. Reports on the InterAtrial Shunt Device (IASD®) and the V­Wave have been published, both of which can be implanted with a low risk and few complications. The V­Wave device is equipped with a valve to prevent paradoxical embolisms. However, paradoxical embolisms were also not observed with the IASD®, and the valve of the V­Wave exhibited considerable degenerative changes and valve closure. Hemodynamic and clinical data of patients with an IASD® or an open V­Wave device demonstrated a sustained hemodynamic improvement. Physical performance capacity and quality of life were increased. Whether IASD® may be broadly applicable in patients with diastolic heart failure is currently under investigation. In selected highly symptomatic patients with diastolic heart failure and PVH, the IASD® is already in clinal use.

[Diagnosis and treatment of aortic valve stenosis]. / Diagnose und Therapie der Aortenklappenstenose.

Aortic valve stenosis (AS) is the most frequently observed valvular heart disease. Once it is symptomatic the mortality rapidly increases. The diagnostic gold standard is transthoracic echocardiography. By measuring the maximum transvalvular velocity, mean transaortic pressure gradient and aortic valve opening area, classification of the type of stenosis can be defined. A differentiation is made between high-gradient AS, low-flow low gradient AS with reduced ventricular ejection fraction (<50%) and the paradoxical low-flow low-gradient AS with preserved ventricular function (≥50%). In some cases, additional diagnostic tools are necessary using dobutamine stress echocardiography, transesophageal echocardiography and cardiac computed tomography. The treatment follows an individualized approach. In cases of indications for valve replacement the multidisciplinary heart team takes into account the patient's age and individual risk for deciding whether an open surgical approach or transcatheter aortic valve implantation is indicated.

[Modern genetic counselling : Practical aspects exemplified by hypertrophic cardiomyopathy]. / Moderne humangenetische Beratung : Praktische Aspekte am Beispiel der hypertrophen Kardiomyopathie.

Genetic counselling and subsequent molecular genetic testing should be performed in patients when an inherited monogenic form of heart disease is suspected. For the individual patient as well as for the (possibly asymptomatic) relatives, molecular diagnostics is important for an early diagnosis, (preventive) therapy and prognosis assessment. Using the example of hypertrophic cardiomyopathy (HCM), the most common monogenic form of structural heart disease, essential aspects of modern genetic counselling are elucidated. Specific examples of one case with a classical form of hypertrophic obstructive cardiomyopathy and one case of congenital HCM with Noonan's syndrome are discussed.

[Response to and further development of the Choosing wisely initiative]. / Resonanz und Weiterentwicklung der Initiative Klug entscheiden.

The Choosing wisely initiative of the German Society of Internal Medicine ("Deutschen Gesellschaft für Innere Medizin," DGIM) and its 12 core focus area specialist societies were brought into being in 2014. The German initiative differs from the American campaign in that it not only considers overuse of diagnostic and therapeutic healthcare services, but also addresses procedures which are frequently not performed although they would bring benefits for patients. Furthermore, the recommendations were approved by an interdisciplinary consensus commission under consideration of all key internal medicine aspects. Since 2014, the initiative has received widespread attention. The 115 recommendations approved by the consensus commission have meanwhile been published in 20 articles. An array of measures were subsequently adopted to further promote the Choosing wisely recommendations ("Klug-entscheiden-Empfehlungen," KEE). These include the systematic incorporation of KEE symposia into DGIM annual congresses and the congresses of the core focus area specialist societies, as well as consideration of the KEE during establishment of future guidelines. Particular attention was paid to the importance of initiating and promoting a research project aimed at familiarizing medical students with the principles and content of the Choosing wisely initiative. The decision for or against specific diagnostic and therapeutic procedures represents an essential medical competence, which should therefore be trained prior to qualification.

Performance of five different bleeding-prediction scores in patients with acute pulmonary embolism.

Bleeding-prediction scores may help guiding management of patients with pulmonary embolism (PE), although no such score has been validated. We aimed to externally validate and compare two bleeding-prediction scores for venous thromboembolism to three scores developed for patients with atrial fibrillation in a real-world cohort of PE patients. We performed a prospective observational cohort study in 448 consecutive PE patients who were treated with heparins followed by vitamin-K-antagonists. The Kuijer, RIETE, HEMORR2HAGES, HAS-BLED and ATRIA scores were assessed at baseline. All patients were followed for the occurrence of major bleeding over a 30-day period. The accuracies of both the overall, original 3-level and newly defined optimal 2-level outcome of the scores were evaluated and compared, both for the 30-day period as well as for bleeding occurring in versus after the first week of treatment. 20 of 448 patients suffered major bleeding resulting in a cumulative incidence of 4.5 % (95 % CI 2.5-6.5). The predictive power of all five scores for bleeding was poor (c-statistics 0.57-0.64), both for the 3-level and 2-level score outcomes. No individual score was found to be superior. The HAS-BLED score had a good c-statistic for bleedings occurring after the first week of treatment (0.75, 95 % CI 0.47-1.0). Current available scoring systems have insufficient accuracy to predict overall anticoagulation-associated bleeding in patients treated for acute PE. To optimally target bleeding-prevention strategies, the development of a high quality PE-specific risk score is urgently needed.

[Choosing wisely together with the patient]. / Gemeinsam mit dem Patienten klug entscheiden.

Within the framework of the Choosing wisely initiative of the German Society for Internal Medicine, all scientific societies associated with internal medicine were requested to highlight the unnecessary or underused medical tests or procedures out of the 60 defined examples, which are of immediate relevance within the doctor-patient interaction. Each of the 12 scientific internal medicine societies compiled and substantiated 2 recommendations. This resulted in a spectrum of important recommendations covering the entire field of internal medicine. In difficult situations these recommendations should contribute to developing and supporting the dialogue with patients on an evidence-based level.

[Choosing wisely in internal medicine]. / Klug entscheiden in der Inneren Medizin.

"Choosing wisely - DGIM" is an initiative of the German Society of Internal Medicine (DGIM) to strengthen the quality of diagnostics and indications for therapy. Aspects of inappropriate patient care are identified based on scientific evidence in collaboration with12 internal medicine and associated societies. Identified aspects are reviewed and endorsed by an interdisciplinary consensus committee. Addressed are those diagnostic and therapeutic measures which are rarely used despite scientific evidence of their usefulness and those which are frequently used although clear evidence exists that the measures are not useful or even harmful. The resulting positive or negative recommendations are intended to support physicians in the assessment of indications. The relevance of the "Choosing wisely - DGIM" initiative is confirmed by a survey involving 4200 members of DGIM.

[Flight and migration : A challenge for medicine in Germany]. / Flucht und Migration : Eine Herausforderung für die Medizin in Deutschland.

In 2015 about 1.1 million refugees came to Germany. As a consequence public health authorities as well as physicians in hospitals and surgeries were faced with considerable challenges and problems. Between January and March 2016 the German Society of Internal Medicine (DGIM) and the Professional Organisation of German Internists (BDI) initiated a survey among their members in order to ascertain which diseases and problems physicians were confronted with. A total of 28,063 members of the DGIM and BDI participated in the survey of which 3626 members answered all questions. This equals a response rate of 11.31 %. Of the respondents, 1865 (51.9 %) stated holding employment positions and 987 (27.4 %) were self-employed. The predominant number of physicians were under the impression that the composition of diseases needing treatment did not change within the time period under survey (55.7 % of employed and 73.7 % of self-employed physicians). Typical disease patterns of internal medicine were mentioned here. Most significant problems when treating migrants and refugees were linguistic communication, cultural affiliation, and psychological traumatic experiences. Little or nothing is known about the modalities of reimbursement for the respective health care areas, especially by physicians in employed positions (84.6 %). In agreement with the vote of the 119th Deutscher Ärztetag, DGIM and BDI recommend the introduction of a nationwide health insurance card for migrants and refugees.

Cardiovascular magnetic resonance feature-tracking assessment of myocardial mechanics: Intervendor agreement and considerations regarding reproducibility.

AIM: To assess intervendor agreement of cardiovascular magnetic resonance feature tracking (CMR-FT) and to study the impact of repeated measures on reproducibility. MATERIALS AND METHODS: Ten healthy volunteers underwent cine imaging in short-axis orientation at rest and with dobutamine stimulation (10 and 20 µg/kg/min). All images were analysed three times using two types of software (TomTec, Unterschleissheim, Germany and Circle, cvi(42), Calgary, Canada) to assess global left ventricular circumferential (Ecc) and radial (Err) strains and torsion. Differences in intra- and interobserver variability within and between software types were assessed based on single and averaged measurements (two and three repetitions with subsequent averaging of results, respectively) as determined by Bland-Altman analysis, intraclass correlation coefficients (ICC), and coefficient of variation (CoV). RESULTS: Myocardial strains and torsion significantly increased on dobutamine stimulation with both types of software (p<0.05). Resting Ecc and torsion as well as Ecc values during dobutamine stimulation were lower measured with Circle (p<0.05). Intra- and interobserver variability between software types was lowest for Ecc (ICC 0.81 [0.63-0.91], 0.87 [0.72-0.94] and CoV 12.47% and 14.3%, respectively) irrespective of the number of analysis repetitions. Err and torsion showed higher variability that markedly improved for torsion with repeated analyses and to a lesser extent for Err. On an intravendor level TomTec showed better reproducibility for Ecc and torsion and Circle for Err. CONCLUSIONS: CMR-FT strain and torsion measurements are subject to considerable intervendor variability, which can be reduced using three analysis repetitions. For both vendors, Ecc qualifies as the most robust parameter with the best agreement, albeit lower Ecc values obtained using Circle, and warrants further investigation of incremental clinical merit.

Increased proatherogenic monocyte-platelet cross-talk in monocyte subpopulations of patients with stable coronary artery disease.

BACKGROUND: Monocytes and platelets are important cellular mediators of atherosclerosis. Human monocytes can be divided into CD14(++) CD16(-) , CD14(++) CD16(+) and CD14(+) CD16(++) cells, which differ in their functional properties. The aim of this study was to examine monocyte subset distribution, monocyte-platelet aggregate (MPA) formation and expression of CCR5, the receptor of the platelet-derived chemokine CCL5, and to determine whether these parameters are altered in individuals with coronary atherosclerosis. METHODS: Peripheral blood cells from 64 healthy blood donors (HBDs) and 60 patients with stable coronary artery disease (CAD) were stained with antibodies against CD14, CD16, CD42b and CCR5 and analysed by flow cytometry. Circulating CCL5 levels were determined using an enzyme-linked immunosorbent assay. RESULTS: In patients with CAD, the relative proportion of the CD14(++) CD16(-) monocyte subset was elevated (P < 0.05) and of the CD14(+) CD16(++) subset was reduced (P < 0.001) compared with the HBD group. Furthermore, MPA formation significantly increased in patients with CAD in all three monocyte subsets. In both study groups, the majority of CCR5(+) cells was detected in CD14(++) CD16(+) monocytes (P < 0.001 versus CD14(++) CD16(-) and CD14(+) CD16(++) ), although the CCR5(+) monocyte number was reduced in patients with CAD (CD14(++) CD16(-) /CD14(+) CD16(++) , P < 0.001; CD14(++) CD16(+) , P < 0.05) compared with the HBD group, particularly in those who were not taking statins. Ex vivo incubation of monocytes from HBDs with plasma from patients with CAD also decreased CCR5(+) expression (P < 0.05 versus plasma from HBDs). Serum CCL5 levels were similar in both groups. CONCLUSIONS: The increased monocyte-platelet cross-talk in patients with CAD might have contributed to atherosclerosis progression. The decreased CCR5(+) monocyte numbers in patients with CAD could have resulted from CCR5(+) cell recruitment into atherosclerotic lesions or CCR5 downregulation in response to circulating factors.

[New pharmaceuticals in cardiology. Heart failure, anticoagulation, dyslipidemia]. / Neue Medikamente in der Kardiologie. Herzinsuffizienz, Antikoagulation, Dyslipidämien.

Three innovative pharmaceuticals which might play an important role in the field of cardiology in the near future were recently tested in large clinical studies. Serelaxin, a vasoactive hormone peptide that is produced during pregnancy, reduces vessel resistance, increases cardiac output, and improves renal function. Lately, it was demonstrated that serelaxin significantly reduces congestion symptoms in patients with acute heart failure. As a secondary endpoint the mortality at day 180 was reduced. Therefore, serelaxin seems to be a promising new drug for the treatment of acute heart failure which might have a prognostic impact. Edoxaban is a selective factor Xa inhibitor, which inhibits thrombin production and thrombus formation. Two recently published studies reported that edoxaban is at least as effective as the vitamin K antagonist warfarin in prevention and treatment of venous thromboembolism and in the prevention of stroke and systemic embolism due to nonvalvular atrial fibrillation. Compared to warfarin, edoxaban significantly exhibited less frequent severe bleeding complications. Edoxaban will probably soon be the fourth new oral anticoagulant available for patients. The serine protease proprotein convertase subtilisin/kexin 9 (PCSK9) reduces the ability of the liver to bind low-density lipoprotein cholesterol (LDL-C) and to remove it from the circulation. Recently, a monoclonal antibody for PCSK9 was developed which induces a LDL-C plasma level reduction up to 73 % and also decreases lipoprotein(a) and apolipoprotein B. PCSK9 inhibition is a promising new mechanism for LDL-C reduction and the corresponding drug will be presumably approved soon by the regulatory authorities.

[Precision medicine enhances personalized medicine in cardiology]. / Präzisionsmedizin vertieft die personalisierte Medizin in der Kardiologie.

Personalized medicine and precision medicine, frequently used synonymously, shall be clearly differentiated. Accordingly, personalization in cardiac medicine is based on the clinical presentation of a patient, as well as his/her cardiovascular risk factors and comorbidities, electrocardiography, imaging, and biomarkers for myocardial load and ischemia. Personalization is based on large clinical trials with detailed subgroup analyses and is practiced on the basis of guidelines. Further in depth personalization is achieved by precision medicine, which is based on innovative imaging for myocardial structure, coronary morphology, and electrophysiology. From the clinical perspective, genome analyses are relevant for comparatively rare monogenetic cardiovascular diseases. While these as well as transcriptome and metabolome analyses play a significant role in cardiovascular research with great translation potential, they have not yet been broadly introduced in the diagnosis, prevention, and treatment of complex cardiovascular diseases. Furthermore, digital technologies have considerable potential in cardiovascular precision medicine. On the one hand, this is based on the frequency of the diseases with the availability of Big Data and, on the other hand, on the availability of bio-signals and sensors of those signals in cardiovascular diseases.