[Short version of the 2nd edition of the German-Austrian S3 guidelines "Cardiogenic shock complicating myocardial infarction-Diagnosis, monitoring and treatment"]. / Kurzversion der 2. Auflage der deutsch-österreichischen S3-Leitlinie "Infarkt-bedingter Kardiogener Schock ­ Diagnose, Monitoring und Therapie".

BACKGROUND: The present guidelines ( http://leitlinien.net ) focus exclusively on cardiogenic shock due to myocardial infarction (infarction-related cardiogenic shock, ICS). The cardiological/cardiac surgical and the intensive care medicine strategies dealt with in these guidelines are essential to the successful treatment and survival of patients with ICS; however, both European and American guidelines on myocardial infarction and heart failure and also position papers on cardiogenic shock focused mainly on cardiological aspects. METHODS: Evidence on the diagnosis, monitoring and treatment of ICS was collected and recommendations compiled in a nominal group process by delegates of the German Cardiac Society (DGK), the German Society for Medical Intensive Care Medicine and Emergency Medicine (DGIIN), the German Society for Thoracic and Cardiovascular Surgery (DGTHG), the German Society for Anaesthesiology and Intensive Care Medicine (DGAI), the Austrian Society for Internal and General Intensive Care Medicine (ÖGIAIM), the Austrian Cardiology Society (ÖKG), the German Society for Prevention and Rehabilitation of Cardiovascular Diseases (DGPR) and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), under the auspices of the Working Group of the Association of Medical Scientific Societies in Germany (AWMF). If only poor evidence on ICS was available, general study results on intensive care patients were inspected and presented in order to enable analogue conclusions. RESULTS: A total of 95 recommendations, including 2 statements were compiled and based on these 7 algorithms with defined instructions on the course of treatment.

[Quality indicators and structural requirements for Cardiac Arrest Centers-Update 2021]. / Qualitätskriterien und strukturelle Voraussetzungen für Cardiac Arrest Zentren ­ Update 2021: Deutscher Rat für Wiederbelebung/German Resuscitation Council (GRC).

An update of the first description of quality indicators and structural requirements for Cardiac Arrest Centers from 2017 based on first experiences and certifications is presented. Criteria were adjusted, substantiated and in some parts redefined for feasibility in everyday clinical use.

High inter- and intra-observer agreement in mapping sequences compared to classical Lake Louise Criteria assessment of myocarditis by inexperienced observers.

AIM: To investigate the observer agreement for the assessment of chronic myocarditis by native T1 and T2 relaxation times, post-contrast T1 relaxation time, and extracellular volume (ECV) fraction, compared to Lake Louise Criteria: oedema ratio (OR) and early gadolinium enhancement ratio (EGEr). MATERIALS AND METHODS: Data were collected retrospectively on 71 consecutive patients who underwent cardiac magnetic resonance imaging as part of a complete diagnostic work-up according to current guidelines for suspected myocarditis. Thirteen cases were excluded due to previous myocardial infarction or technical issues. To test for intra- and interobserver agreement, the determination of the myocardial native T1 and T2 relaxation times, post-contrast T1 relaxation time, ECV, OR and EGEr was undertaken by two medical school graduates after comprehensive training. Bland-Altman analysis and intraclass correlation coefficient (ICC) were assessed. RESULTS: The final analysis included 27 patients with chronic myocarditis, 21 patients with dilated cardiomyopathy and/or hypertensive heart disease, and 10 patients with unremarkable investigations in the control group. Excellent interobserver agreement was obtained for native T1 and T2 relaxation times, post-contrast T1 relaxation time and ECV, with ICC of 0.982/0.977/0.991/0.994, p < 0.001. Interobserver agreement was lower for OR and EGEr, with ICC of 0.841 and 0.818, p < 0.001, respectively. Mapping parameters (cut-off values: T1 1,070 ms, T2 54 ms, ECV 30%) yield good performance in the diagnosis of chronic myocarditis with the best sensitivity/specificity/accuracy of 93%/80%/88% for ECV, followed by 70%/80%/74% for T2, and 52%/88%/69% for T1. CONCLUSIONS: mapping parameters show excellent agreement between observers in the assessment of myocarditis.

[Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR) : Consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC]. / Empfehlungen zur extrakorporalen kardiopulmonalen Reanimation (eCPR) : Konsensuspapier der DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI und GRC.

Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible etiology. Currently there are no randomized, controlled studies on eCPR, and valid predictors of benefit and outcome which might guide the indication for eCPR are lacking. Currently selection criteria and procedures differ across hospitals and standardized algorithms are lacking. Based on expert opinion, the present consensus statement provides a proposal for a standardized treatment algorithm for eCPR.

Genetic heterogeneity in Pakistani microcephaly families revisited.

Autosomal recessive primary microcephaly (MCPH) is a rare and heterogeneous genetic disorder characterized by reduced head circumference, low cognitive prowess and, in general, architecturally normal brains. As many as 14 different loci have already been mapped. We recruited 35 MCPH families in Pakistan and could identify the genetic cause of the disease in 31 of them. Using homozygosity mapping complemented with whole-exome, gene panel or Sanger sequencing, we identified 12 novel mutations in 3 known MCPH-associated genes - 9 in ASPM, 2 in MCPH1 and 1 in CDK5RAP2. The 2 MCPH1 mutations were homozygous microdeletions of 164,250 and 577,594 bp, respectively, for which we were able to map the exact breakpoints. We also identified four known mutations - three in ASPM and one in WDR62. The latter was initially deemed to be a missense mutation but we demonstrate here that it affects splicing. As to ASPM, as many as 17 out of 27 MCPH5 families that we ascertained in our sample were found to carry the previously reported founder mutation p.Trp1326*. This study adds to the mutational spectra of four known MCPH-associated genes and updates our knowledge about the genetic heterogeneity of MCPH in the Pakistani population considering its ethnic diversity.

Morphological alterations in two siblings with autosomal recessive congenital ichthyosis associated with CYP4F22 mutations.

Autosomal recessive congenital ichthyosis (ARCI) caused by mutations in CYP4F22 is very rare. CyP4F22, a protein of the cytochrome-P450 family 4, encodes an epidermal ω-hydroxylase decisive in the formation of acylceramides, which is hypothesized to be crucial for skin-barrier function. We report a girl with consanguineous parents presenting as collodion baby with contractures of the great joints and palmoplantar hyperlinearity. In the course of the disease she developed fine scaling of the skin with erythroderma, the latter disappearing until the age of 6 months. Her sister showed a generalized fine-scaling phenotype, and, interestingly, was born without a collodion membrane. The analysis of all known candidate genes for ARCI in parallel with a next-generation sequencing approach using a newly designed dermatogenetics gene panel revealed a previously unknown homozygous splice-site mutation c.549+5G>C in CYP4F22 in both girls, confirming the diagnosis of ARCI. Ultrastructural analysis by transmission electron microscopy in both patients showed epidermal hyperplasia, orthohyperkeratosis with persistence of corneodesmosomes into the outer stratum corneum layers, fragmented and disorganized lamellar lipid bilayers, which could be ascribed to inhomogeneous lamellar body secretion, as well as lamellar body and lipid entombment in the corneocytes. These findings correlated with increased transepidermal water loss on the functional level. For the first time, we report a collodion baby phenotype and epidermal barrier impairment in CyP4F22-deficient epidermis at both the ultrastructural and functional level, and corroborate the importance of CyP4F22 for epidermal maturation and barrier function.

[Cardiogenic shock : Current evidence]. / Kardiogener Schock : Aktuelle Evidenz.

This CME article addresses the pathophysiology, incidence, current survival outcome and treatment options for patients with cardiogenic shock as a complication of acute myocardial infarction. The shock spiral of left heart failure due to cardiac infarction, subsequent vasoconstriction and paradoxical vasodilation due to the systemic inflammation response syndrome (SIRS) is a vicious circle which must be interrupted. Treatment focuses on the evidence from randomized clinical trials and the current guideline recommendations. With respect to interventional and surgical treatment the question of culprit lesion vs. complete revascularization is still unsolved. For medicinal treatment acetylsalicylic acid (ASA) and heparin are more often supplemented with prasugrel and ticagrelor. In the case of inotropes, dobutamine remains the first-line treatment option and for vasopressors norepinephrine. The calcium sensitizer levosimendan has not provided the hoped for superiority over conventional treatment in randomized trials. The use of intra-aortic balloon pumps (IABP) is no longer recommended as circulatory support in acute heart failure (reduced to class III). The use of percutaneous implantable mechanical circulatory support devices has not shown a survival benefit in the few randomized trials carried out so far even when compared with IABP, due to increased bleeding complications.

Treatment of asymptomatic aortic valve stenosis : Watchful waiting or early intervention?

There is ongoing debate about the optimal management of severe asymptomatic aortic stenosis (AS). Thus far, current guidelines recommend a watchful waiting strategy for the majority of asymptomatic patients. However, data on the prognosis of asymptomatic AS are inconsistent. Some reports claim an increased risk of complications and even mortality in this subset of patients when treated conservatively. Several factors are considered to contribute to the impaired outcome of asymptomatic patients, such as progressive myocardial damage or sudden cardiac death, during the watchful waiting period. Indeed, a few nonrandomized studies are available in the literature showing improved survival with early aortic valve replacement during the asymptomatic phase compared with watchful waiting. However, these studies have several limitations particularly with regard to methodology, and thus making a clear recommendation on treatment options impossible. Therefore, randomized controlled trials are urgently needed in order to treat these patients on the basis of adequate evidence.

[Acute myocardial infarction in patients with ST-segment elevation myocardial infarction : ESC guidelines 2017]. / Akuter Myokardinfarkt bei Patienten mit ST-Strecken-Hebungs-Infarkt : ESC-Leitlinien 2017.

This article gives an update on the management of acute ST-segment elevation myocardial infarction (STEMI) according to the recently released European Society of Cardiology guidelines 2017 and the modifications are compared to the previous STEMI guidelines from 2012. Primary percutaneous coronary intervention (PCI) remains the preferred reperfusion strategy. New guideline recommendations relate to the access site with a clear preference for the radial artery, use of drug-eluting stents over bare metal stents, complete revascularization during the index hospitalization, and avoidance of routine thrombus aspiration. For periprocedural anticoagulation during PCI, bivalirudin has been downgraded. Oxygen treatment should be administered only if oxygen saturation is <90%. In cardiogenic shock, intra-aortic balloon pumps should no longer be used. New recommendations are in place with respect to the duration of dual antiplatelet therapy for patients without bleeding events during the first 12 months. Newly introduced sections cover myocardial infarction with no relevant stenosis of the coronary arteries (MINOCA), the introduction of new indicators for quality of care for myocardial infarction networks and new definitions for the time to reperfusion.

Interventional therapies in acute myocardial infarction complicated by cardiogenic shock.

Cardiogenic shock remains the most common cause of death in patients with acute myocardial infarction. Early revascularization of the infarct-related artery has been shown to reduce mortality and is the therapeutic cornerstone. The optimal revascularization strategy of additional non-culprit lesions remains yet to be determined. Further, uncertainties exist with respect to access site choice, antiplatelet regimen as well as mechanical support devices. This review outlines current evidence on the interventional management of cardiogenic shock complicating acute myocardial infarction.

[Thrombus aspiration in patients with acute myocardial infarction : Scientific evidence and guideline recommendations]. / Thrombusaspiration bei Patienten mit akutem Myokardinfarkt : Wissenschaftliche Evidenz und Empfehlungen in den Leitlinien.

Recent advances in percutaneous coronary intervention and antiplatelet therapy as well as faster door-to-balloon times have markedly improved the therapy of patients with acute myocardial infarction. However, impaired myocardial perfusion despite revascularization of the infarcted vessel remains an ongoing problem with high prognostic relevance. In initial clinical trials thrombus aspiration in addition to conventional percutaneous coronary intervention demonstrated benefits regarding coronary flow and myocardial perfusion and was therefore recommended in practice guidelines. These improvements in surrogate endpoints did not translate into a favorable clinical outcome in recent large-scale multicenter randomized trials investigating the routine use of thrombus aspiration in patients with acute myocardial infarction. Furthermore, an increased risk of stroke after thrombus aspiration raises safety concerns. Therefore, thrombus aspiration has been downgraded in the recent guideline updates. The current article reviews the evidence from clinical trials and the recommendations in practice guidelines regarding thrombus aspiration in acute myocardial infarction.

Left ventricular global function index assessed by cardiovascular magnetic resonance for the prediction of cardiovascular events in ST-elevation myocardial infarction.

BACKGROUND: The left ventricular performance index (LVGFI) as a comprehensive marker of cardiac performance integrates LV structure with global function within one index. In a prospective cohort study of healthy individuals the LVGFI demonstrated a superior prognostic value as compared to LV ejection fraction (LVEF). In patients after ST-segment elevation myocardial infarction (STEMI), however, the role of the LVGFI is unknown. Aim of this study was to investigate the relationship between the LVGFI and infarct characteristics as well as prognosis in a large multicenter STEMI population. METHODS: In total 795 STEMI patients reperfused by primary angioplasty (<12 h after symptom onset) underwent cardiovascular magnetic resonance (CMR) at 8 centers. CMR was completed within one week after infarction using a standardized protocol including LV dimensions, mass and function for calculation of the LVGFI. The primary clinical endpoint of the study was the occurrence of major adverse cardiac events (MACE). RESULTS: The median LVGFI was 31.2 % (interquartile range 25.7 to 36.6). Patients with LVGFI < median had significantly larger infarcts, less myocardial salvage, a larger extent of microvascular obstruction, higher incidence of intramyocardial hemorrhage and more pronounced LV dysfunction (p < 0.001 for all). MACE and mortality rates were significantly higher in the LVGFI < median group (p < 0.001 and p = 0.003, respectively). The LVGFI had an incremental prognostic value in addition to LVEF for prediction of all-cause mortality. CONCLUSIONS: The LVGFI strongly correlates with markers of severe myocardial and microvascular damage in patients with STEMI, offering prognostic information beyond traditional cardiac risk factors including the LVEF. TRIALS REGISTRATION: ClinicalTrials.gov: NCT00712101.

Clinical and genetic findings in a family with NMNAT1-associated Leber congenital amaurosis: case report and review of the literature.

BACKGROUND: Leber congenital amaurosis (LCA) is a severe retinal dystrophy, typically manifesting in the first year of life. Mutations in more than 18 genes have been reported to date. In recent studies, biallelic mutations in NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 have been found to cause LCA. PURPOSE: To broaden the knowledge regarding the phenotype of NMNAT1-associated LCA. METHODS: Clinical ophthalmologic examinations were performed in two sisters with LCA. Whole exome sequencing was performed in one of the affected girls, with subsequent segregation analysis in the affected sister and unaffected parents. The literature was reviewed for reports of NMNAT1-associated LCA. RESULTS: Exome sequencing revealed the known NMNAT1 mutation c.25G>A (p.Val9Met) in a homozygous state. Segregation analysis showed the same homozygous mutation in the affected younger sister. Both parents were found to be heterozygous carriers of the mutation. The two girls both presented with severe visual impairment, nystagmus, central atrophy of the pigment epithelium, and pigment clumping in the periphery before the age of 6 months. Retinal vessels were attenuated. Both children were hyperopic. In the older sister, differential diagnosis included an inflammatory origin, but electrophysiology in her as well as her sister confirmed a diagnosis of LCA. Pallor of the optic nerve head was not present at birth but developed progressively. CONCLUSIONS: We confirmed a diagnosis of NMNAT1-associated LCA in two siblings through identification of the mutation (c.25G>A [p. Val9Met]) in a homozygous state. In infants with non-detectable electroretinogram (ERG), along with severe congenital visual dysfunction or blindness and central pigment epithelium atrophy with pigment clumping resembling scarring due to chorioretinitis, LCA due to NMNAT1 mutations should be considered.

[ESC guidelines 2015. Non-ST-elevation acute coronary syndrome]. / ESC-Leitlinien 2015. Akutes Koronarsyndrom ohne ST-Strecken-Hebung.

In August 2015 the European Society of Cardiology (ESC) published new guidelines for the management of acute coronary syndrome in patients presenting without persistent ST-segment elevation, which incorporate the scientific progress since 2011. The innovation with probably the most impact on the clinical practice is the introduction of 0 h/1 h protocols for exclusion or inclusion of myocardial infarction without ST-segment elevation. These 0 h/1 h protocols are equally recommended to the established 0 h/3 h protocol. For these protocols blood is drawn on admission and 1 h later and the troponin level is analyzed by means of highly sensitive troponin assays. Troponin cut-off values were validated in several large studies, therefore, now facilitating a faster exclusion of myocardial infarction with an equal negative predictive value to 3 h protocols. Additionally, access via the radial artery is recommended over a femoral artery access for coronary angiography and when necessary the subsequent coronary intervention. Other novel aspects apply to the anti-ischemic and anti-thrombotic medication.

[Mechanical support in cardiogenic shock]. / Mechanische Unterstützung im kardiogenen Schock.

Treatment of patients in cardiogenic shock (CS) presenting with acute myocardial infarction (AMI) is still a challenge and mortality rates remain high, approaching 50 %. Hemodynamic stabilization before and/or after early revascularization remains the primary goal in these patients. In addition to hemodynamic support by inotropes and vasopressors, support with mechanical devices such as intra-aortic balloon pumping (IABP), percutaneous left ventricular assist devices (LVAD) and complete extracorporeal life support (ECLS) with extracorporeal membrane oxygenation (ECMO) may be considered. The use of IABP cannot be recommended anymore on a routine basis. Unfortunately, there are no large randomized data from studies evaluating treatment with mechanical support systems compared to standard treatment with respect to the clinical outcome of patients and no head-to-head comparison of different devices is available. Another important open question to be answered is which subgroups of patients may have a benefit from LVAD therapy. Guidelines discourage the routine use of mechanical support as a first-line treatment in CS patients and emphasize that the application should be restricted to those patients with refractory shock. This article gives an overview of the different devices for percutaneous mechanical support in CS and describes the available evidence and guideline recommendations.

[Antiplatelet therapy and anticoagulation in acute coronary syndrome: current evidence]. / Plättchenhemmung und Antikoagulation beim akuten Koronarsyndrom: Aktuelle Evidenz.

In recent years, the prognosis of patients with an acute coronary syndrome (ACS) has significantly improved. This can mainly be attributed to the implementation of primary percutaneous coronary intervention (PCI). Apart from mechanical reperfusion, an optimal medical strategy is of great importance. Antiplatelet and antithrombotic therapies in particular play a crucial role in the management of patients with ACS. New options in antiplatelet therapy are more potent P2Y12 inhibitors in addition to acetylsalicylic acid and clopidogrel. Furthermore, anticoagulant therapy before, during and after PCI can be performed by the use of unfractionated heparin, low molecular weight heparins, such as enoxaparin, the synthetic pentasaccharide fondaparinux and the direct thrombin inhibitor bivalirudin with or without additional administration of glycoprotein IIb/IIIa inhibitors. In this article, data on antiplatelet and anticoagulant therapy are presented and the current evidence is discussed.

[Management of acute myocardial infarction with ST-segment elevation: Update 2013]. / Management des akuten ST-Strecken-Hebungsinfarktes: Update 2013.

This article gives an update on the management of ST-segment elevation myocardial infarction (STEMI) according to guidelines released in 2012 by the European Society of Cardiology. To ensure a reliable diagnosis the updated universal definition of myocardial infarction will also be covered which is defined by myocardial necrosis. Criteria for diagnosis are a rise or fall of cardiac biomarkers, preferably troponin, in conjunction with symptoms of myocardial ischemia, new repolarisation disorders or left bundle branch block, development of pathological Q-waves, new hypokinesia/akinesia or loss in viability or the detection of intracoronary thrombi during cardiac catheterization or autopsy. The current recommendations for primary diagnosis and treatment by the first medical contact will also be discussed and contains decision-making for the optimal reperfusion strategy. Primary percutaneous coronary intervention remains the preferred reperfusion strategy; however, specifications with respect to time for diagnosis and reperfusion have been introduced. Furthermore, establishing a STEMI network has been emphasized in more detail. Special attention is paid to the new antiplatelet agents and anticoagulation therapy where prasugrel and ticagrelor are currently preferred over clopidogrel.

Is percutaneous coronary intervention as effective as bypass surgery in left main stem coronary artery stenosis?

Recent advances in percutaneous coronary intervention (PCI) have rekindled interest in this treatment modality also in the setting of unprotected left main stenosis. Randomized trials reported a similar risk of death or myocardial infarction between PCI and coronary artery bypass grafting (CABG). However, rates of stroke were higher after CABG, whereas patients undergoing PCI had a higher risk of repeat revascularization. Although CABG remains the standard of care for left main stenosis in current guideline recommendations, PCI is considered a reasonable alternative in patients with low to intermediate anatomical complexity and at increased surgical risk. An interdisciplinary assessment is indispensable in order to choose the best treatment option for each individual patient.