[Legal aspects in digital cardiology]. / Rechtliche Aspekte in der digitalen Kardiologie.

Digital assistants have become an indispensable tool in modern cardiology. The associated technological progress offers a significant potential to increase the efficiency of medical processes, enable more precise diagnoses in a shorter time, and thus improve patient care. However, the integration of digital assistants into clinical cardiology also raises new challenges and questions, particularly regarding the handling of legal issues. This review article aims to raise awareness of individual legal issues resulting from the use of digital technologies in cardiology. The focus is on how to deal with various legal challenges that cardiologists face, including issues related to treatment freedom, professional confidentiality and data protection. The integration of digital assistants in cardiology leads to a noticeable improvement in efficiency and quality of patient care, but at the same time, it involves a variety of legal challenges that need to be carefully addressed.

[Antiarrhythmic drugs in the present day]. / Antiarrhythmika in der heutigen Zeit.

Cardiac arrhythmias cause a significant proportion of hospitalizations and physician contacts worldwide. By using antiarrhythmic drugs, cardiac arrhythmias can be effectively treated and the frequency of recurrences reduced. Atrial fibrillation and heart failure represent diseases in which antiarrhythmic drugs are more often used on a long-term basis. The aim of this article is to provide an overview of the most common antiarrhythmic drugs and their uses as well as to provide recommendations for adequate handling and use, especially in the outpatient setting. In addition to long-term use, some antiarrhythmic drugs are also administered for the acute management of supraventricular or ventricular tachycardia. Relevant contraindications, side effects and interactions must be considered, meaning that patients should be followed up when using these potent drugs. This article shows in detail what to consider when using antiarrhythmic drugs in order to ensure not only effective but also safe treatment.

Vasodilator reactive oxygen species ameliorate perturbed myocardial oxygen delivery in exercising swine with multiple comorbidities.

Multiple common cardiovascular comorbidities produce coronary microvascular dysfunction. We previously observed in swine that a combination of diabetes mellitus (DM), high fat diet (HFD) and chronic kidney disease (CKD) induced systemic inflammation, increased oxidative stress and produced coronary endothelial dysfunction, altering control of coronary microvascular tone via loss of NO bioavailability, which was associated with an increase in circulating endothelin (ET). In the present study, we tested the hypotheses that (1) ROS scavenging and (2) ETA+B-receptor blockade improve myocardial oxygen delivery in the same female swine model. Healthy female swine on normal pig chow served as controls (Normal). Five months after induction of DM (streptozotocin, 3 × 50 mg kg-1 i.v.), hypercholesterolemia (HFD) and CKD (renal embolization), swine were chronically instrumented and studied at rest and during exercise. Sustained hyperglycemia, hypercholesterolemia and renal dysfunction were accompanied by systemic inflammation and oxidative stress. In vivo ROS scavenging (TEMPOL + MPG) reduced myocardial oxygen delivery in DM + HFD + CKD swine, suggestive of a vasodilator influence of endogenous ROS, while it had no effect in Normal swine. In vitro wire myography revealed a vasodilator role for hydrogen peroxide (H2O2) in isolated small coronary artery segments from DM + HFD + CKD, but not Normal swine. Increased catalase activity and ceramide production in left ventricular myocardial tissue of DM + HFD + CKD swine further suggest that increased H2O2 acts as vasodilator ROS in the coronary microvasculature. Despite elevated ET-1 plasma levels in DM + HFD + CKD swine, ETA+B blockade did not affect myocardial oxygen delivery in Normal or DM + HFD + CKD swine. In conclusion, loss of NO bioavailability due to 5 months exposure to multiple comorbidities is partially compensated by increased H2O2-mediated coronary vasodilation.

The Heart Failure Optimization Study (HF-OPT): rationale and design.

BACKGROUND: According to the current guidelines, implantable cardioverter-defibrillators (ICD) for primary prevention in patients with heart failure and reduced ejection fraction (HFrEF) should not be considered until optimal guideline-directed medical therapy (GDMT) has been achieved for a minimum of 3 months. Optimization of GDMT often needs time beyond 3 months after diagnosis. The aim of the Heart Failure Optimization Study (HF-OPT) is to evaluate the recovery of left ventricular function beyond 3 months after diagnosis of newly diagnosed HFrEF. METHODS: The HF-OPT multicenter study is comprised of two non-randomized phases (registry and study). During the first 90 days a wearable cardioverter-defibrillator (WCD) is prescribed and patients are enrolled in an observational pre-study registry. Registry subjects meeting inclusion criteria for the study portion at day 90 have ongoing left ventricular ejection fraction (LVEF) reassessment at 90, 180 and 360 days after the index hospital discharge, regardless of continued WCD use. Approximately 600 subjects will be enrolled in the study portion. Of those, one-third are anticipated to start the study phase at day 90 with reduced LVEF. The primary objective of this study is to observe the rate of recovery of LVEF > 35% between 90 and 180 days, while key secondary endpoints include mortality and WCD recorded arrhythmias and shocks. DISCUSSION: The HF-OPT study will provide important information on the rate of additional recovery of LVEF > 35%, between 90 and 180 days, in newly diagnosed HF with reduced LVEF patients being titrated with GDMT. The results of the study may impact indications for primary prophylactic ICD implantation.

Questionnaire survey on cardiologists' view and management of coronary microvascular disease in clinical practice.

OBJECTIVE: We aimed to assess the opinion of Dutch cardiologists on coronary microvascular disease (CMD) and its management in clinical practice, and to assess the need for a CMD guideline among Dutch cardiologists. METHODS: We developed an online questionnaire including different aspects of CMD which was reviewed by an expert panel. The questionnaire was distributed by e­mail among all members of the Dutch Society of Cardiology. RESULTS: A total of 103 cardiologists (70% male) completed the questionnaire (response rate: 10%). Median age and years of experience as a cardiologist were 49 ± 15 and 12 ± 12 years, respectively. Overall, 93% of the cardiologists had considered the CMD diagnosis, 85% had ever made such a diagnosis, 90% had treated a patient with CMD, and 61% had referred patients to tertiary care. The median (interquartile range) self-rated knowledge level was 7.0 (2.0) (scale of 0-10). 84% rated their knowledge as sufficient (>5.5) and 58% viewed CMD as a disease entity. Overall, 61% and 17%, respectively, agreed that evidence-based diagnostic and treatment modalities for CMD do not exist, while 56% believed that CMD patients have a higher risk for cardiovascular disease and mortality. Finally, 82% of the responders stated that a CMD guideline is needed, and 91% wanted to receive the guideline once developed. DISCUSSION: Fifty-eight per cent of the responders recognise CMD as a separate disease entity. Our study underscores the need for a dedicated CMD guideline for Dutch cardiology practice. However, the response rate was low (10%), and it is likely that mainly cardiologists interested in CMD have participated in our study.

[Multipoint pacing-more CRT or a waste of battery power?] / MultiPoint-Pacing ­ mehr CRT oder Batterieverschwendung?

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with broad QRS complex ≥130 ms and heart failure with reduced ejection fraction despite optimal guideline-directed medical therapy. However, approximately 30% of the patients implanted with a CRT system do not show clinical benefit. Reasons for nonresponse are complex and some aspects can be addressed during follow-up. Based on quadripolar lead technology, multipoint pacing (MPP) allows left ventricular stimulation at two different sites along the lead. In particular, in scarred and fibrotic ventricular myocardium stimulation at two different sites may overcome conduction barriers and lead to homogeneous ventricular depolarization. Especially for patients that do not respond to conventional CRT, activation of MPP may present an option to increase clinical response. On the other hand, MPP may significantly decrease battery longevity.This review offers an overview of the current knowledge and data on MPP balancing the potential clinical benefit and the possible disadvantages of this therapy.

Device therapy in heart failure with reduced ejection fraction-cardiac resynchronization therapy and more.

In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology. However, the vast majority of heart failure patients show a narrow QRS complex or a non-LBBB morphology. These patients are not candidates for CRT and alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) may be considered. BAT modulates vegetative dysregulation in heart failure. CCM improves contractility, functional capacity, and symptoms. Although a broad data set is available for BAT and CCM, mortality data are still lacking for both methods. This article provides an overview of the device-based therapeutic options for patients with HFrEF.

[Ventricular arrhythmias : What has been confirmed in therapy?] / Ventrikuläre Herzrhythmusstörungen : Was ist gesichert in der Therapie?

Ventricular arrhythmias include a wide range of potentially benign single ventricular premature contractions to ventricular tachycardia and ventricular fibrillation with a risk for sudden cardiac death. The diagnosis of ventricular arrhythmia is made by 12-lead electrocardiogram, 24 h Holter monitoring, an external or implantable loop recorder, or during in-hospital monitoring. Especially the diagnosis of wide complex tachycardias is challenging in terms of differentiating between ventricular tachycardia and supraventricular tachycardia with aberrant atrioventricular conduction. After documentation of ventricular arrhythmias, diagnostic work-up with respect to structural or electrical cardiomyopathy is mandatory followed by risk stratification for sudden cardiac death. Therapeutic options for treatment of ventricular arrhythmias range from pharmacological therapy and interventional procedures such as catheter ablation and implantable devices. The current article provides an overview of the diagnosis of ventricular tachycardia and underlying cardiomyopathies. Furthermore, medical and interventional therapies are described. In addition, the indications for implantable and wearable defibrillators are presented.

CECR1-mediated cross talk between macrophages and vascular mural cells promotes neovascularization in malignant glioma.

Glioblastomas (glioblastoma multiforme, GBM) are most malignant brain tumors characterized by profound vascularization. The activation of macrophages strongly contributes to tumor angiogenesis during GBM development. Previously, we showed that extracellular adenosine deaminase protein Cat Eye Syndrome Critical Region Protein 1 (CECR1) is highly expressed by M2-like macrophages in GBM where it defines macrophage M2 polarization and contributes to tumor expansion. In this study, the effect of CECR1 in macrophages on tumor angiogenesis was investigated. Immunohistochemical evaluation of GBM tissue samples showed that the expression of CECR1 correlates with microvascular density in the tumors, confirming data from the TCGA set. In a three-dimensional co-culture system consisting of human pericytes, human umbilical vein endothelial cells and THP1-derived macrophages, CECR1 knockdown by siRNA and CECR1 stimulation of macrophages inhibited and promoted new vessel formation, respectively. Loss and gain of function studies demonstrated that PDGFB mRNA and protein levels in macrophages are modulated by CECR1. The proangiogenic properties of CECR1 in macrophages were partially mediated via paracrine activation of pericytes by PDGFB-PDGFRß signaling. CECR1-PDGFB-PDGFRß cross-activation between macrophages and pericytes promoted pericyte migration, shown by transwell migration assay, and enhanced expression and deposition of periostin, a matrix component with proangiogenic properties. CECR1 function in (M2-like) macrophages mediates cross talk between macrophages and pericytes in GBM via paracrine PDGFB-PDGFRß signaling, promoting pericyte recruitment and migration, and tumor angiogenesis. Therefore, CECR1 offers a new portent target for anti-angiogenic therapy in GBM via immune modulation.

Efficacy and safety of durotomy after decompressive hemicraniectomy in traumatic brain injury.

Decompressive hemicraniectomy (DH) plus duroplasty was demonstrated to be effective for treating critically elevated intracranial pressure (ICP). In order to shorten operation time and to avoid the use of autologous or heterologous material, durotomy has been introduced as an alternative to duroplasty. Only limited data is available on the effect of DH and durotomy on the increased ICP in traumatic brain injury (TBI). Therefore, we collected consecutive intraoperative ICP readings during the different steps of DH and durotomy in TBI patients. Eighteen patients with TBI and uncontrollable ICP increase (measured by either an intraparenchymal or an intraventricular ICP probe) underwent DH and durotomy. ICP readings as well as mean arterial blood pressure (MAP) and arterial PCO2 were obtained during defined stages of the operation. Surgical complications of the durotomy itself and of cranioplasty after 3 months were recorded. The outcome was assessed prior to cranioplasty using the Glasgow Outcome Scale (GOS). ICP dropped significantly during surgery from a mean of 41 ( ± 16.2) mmHg at the beginning to a mean of 11.8 ( ± 7.5) mmHg at the end (p ≤ 0.001). A first significant ICP-decrease to a mean of 18 ( ± 10.8) mmHg (p ≤ 0.001) was detected after removal of the bone flap, and a second significant ICP-decrease to a mean of 10.6 ( ± 5.3) mmHg (p < 0.001) during durotomy. The mean operation time was 115.3 min ( ± 49.6). Five patients (28%) died; seven patients (39%) had a good outcome (GOS 5). There were no relevant complications associated to durotomy. Durotomy after DH is a safe and straightforward procedure, which significantly lowers critically increased ICP in patients with TBI. Although no graft is used, dural preparation for cranioplasty at 3 months is easily possible.

[The wearable cardioverter/defibrillator : Temporary protection from sudden cardiac death]. / Die Defibrillatorweste : Passagerer Schutz vor dem plötzlichen Herztod.

In the majority of cases sudden cardiac death (SCD) is caused by ventricular tachyarrhythmia. Implantable cardioverter-defibrillators (ICD) represent an evidence-based and established method for prevention of SCD. For patients who do not fulfill the criteria for guideline-conform implantation of an ICD but still have an increased, e.g. transient risk for SCD, a wearable cardioverter-defibrillator (WCD) vest was developed to temporarily prevent SCD. Numerous studies have shown the safety and efficacy of the WCD, although there is still a gap in evidence concerning a reduction in overall mortality and improvement in prognosis. This article gives an overview on the currently available literature on WCD, the indications, potential risks and complications.

Animal models of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) constitutes a clinical syndrome in which the diagnostic criteria of heart failure are not accompanied by gross disturbances of systolic function, as assessed by ejection fraction. In turn, under most circumstances, diastolic function is impaired. Although it now represents over 50 % of all patients with heart failure, the mechanisms of HFpEF remain understood, precluding effective therapy. Understanding the pathophysiology of HFpEF has been restricted by both limited access to human myocardial biopsies and by the lack of animal models that fully mimic human pathology. Animal models are valuable research tools to clarify subcellular and molecular mechanisms under conditions where the comorbidities and other confounding factors can be precisely controlled. Although most of the heart failure animal models currently available represent heart failure with reduced ejection fraction, several HFpEF animal models have been proposed. However, few of these fulfil all the features present in human disease. In this review we will provide an overview of the currently available models to study HFpEF from rodents to large animals as well as present advantages and disadvantages of these models.

Peripheral arterial tonometry cannot detect patients at low risk of coronary artery disease.

BACKGROUND: Endothelial dysfunction precedes coronary artery disease (CAD) and can be measured by peripheral arterial tonometry (PAT). We examined the applicability of PAT to detect a low risk of CAD in a chest pain clinic. METHODS: In 93 patients, PAT was performed resulting in reactive hyperaemia (RHI) and augmentation (AIx) indices. Patients were risk classified according to HeartScore, Diamond and Forrester pretest probability (DF), exercise testing (X-ECG), and computed tomography calcium scoring (CCS) and angiography (CTA). Correlations, risk group differences and prediction of revascularisation within 1 year were calculated. RESULTS: RHI correlated with HeartScore (r = - 0.21, p = 0.05), AIx with DF (r = 0.26, p = 0.01). However, both were not significantly different between normal and ischaemic X-ECG groups. In addition RHI and AIx were similar between low risk as compared with intermediate-to-high risk, based on risk algorithms (RHI: 1.98 (0.67) vs 1.94 (0.78); AIx: 0.0 (21) vs 5.0 (25); p = NS), or CCS and CTA (RHI: 1.99 (0.58) vs 1.89 (0.82); AIx: - 2.0 (24) vs 4.0 (25); p = NS). Finally, RHI and AIx failed to predict revascularisation (RHI: OR 1.42, CI 0.65-3.1; AIx: OR 1.02, CI 0.98-1.05). CONCLUSIONS: PAT cannot detect a low risk of CAD, possibly because RHI and AIx versus X-ECG, CCS and CTA represent independent processes.

[Primary and secondary prophylactic ICD therapy in congenital electrical and structural cardiomyopathies]. / ICD-Therapie zur Primär- und Sekundärprophylaxe kongenitaler arrhythmogener Erkrankungen.

Congenital electrical and structural cardiomyopathies are rare and associated with an increased risk for syncope and sudden cardiac death in the young. Due to the young age of the patients and the limited data available, risk stratification and especially ICD therapy are challenging. In this young patient collective, ICD therapy is associated with a high complication rate, which does not justify unreserved primary prophylactic ICD implantation. The aim of this review is to elucidate risk stratification and ICD therapy of various electrical and structural cardiomyopathies.

The impact of Fourier-Domain optical coherence tomography catheter induced motion artefacts on quantitative measurements of a PLLA-based bioresorbable scaffold.

Intracoronary Fourier-Domain optical coherence tomography (FD-OCT) enables imaging of the coronary artery within 2-4 seconds, a so far unparalleled speed. Despite such fast data acquisition, cardiac and respiratory motion can cause artefacts due to longitudinal displacement of the catheter within the artery. We studied the influence of longitudinal FD-OCT catheter displacement on serial global lumen and scaffold area measurements in coronary arteries of swine that received PLLA-based bioresorbable scaffolds. In 10 swine, 20 scaffolds (18 × 3.0 mm) were randomly implanted in two epicardial coronary arteries. Serial FD-OCT imaging was performed immediately after implantation (T1) and at 3 (T2) and 6 months (T3) follow-up. Two methods for the selection of OCT cross-sections were compared. Method A did not take into account longitudinal displacement of the FD-OCT catheter. Method B accounted for longitudinal displacement of the FD-OCT catheter. Fifty-one OCT pullbacks of 17 scaffolds were serially analyzed. The measured scaffold length differed between time points, up to one fourth of the total scaffold length, indicating the presence of longitudinal catheter displacement. Between method A and B, low error was demonstrated for mean area measurements. Correlations between measurements were high: R2 ranged from 0.91 to 0.99 for all mean area measurements at all time points. Considerable longitudinal displacement of the FD-OCT catheter was observed, diminishing the number of truly anatomically matching cross-sections in serial investigations. Global OCT dimensions such as mean lumen and scaffold area were not significantly affected by this displacement. Accurate co-registration of cross-sections, however, is mandatory when specific regions, e.g. jailed side branch ostia, are analyzed.