Coronary intravascular lithotripsy and rotational atherectomy for severely calcified stenosis: Results from the ROTA.shock trial.

BACKGROUND: Severely calcified coronary lesions present a particular challenge for percutaneous coronary intervention. AIMS: The aim of this randomized study was to determine whether coronary intravascular lithotripsy (IVL) is non-inferior to rotational atherectomy (RA) regarding minimal stent area (MSA). METHODS: The randomized, prospective non-inferiority ROTA.shock trial enrolled 70 patients between July 2019 and November 2021. Patients were randomly (1:1) assigned to undergo either IVL or RA before percutaneous coronary intervention of severely calcified coronary lesions. Optical coherence tomography was performed at the end of the procedure for primary endpoint analysis. RESULTS: The primary endpoint MSA was lower but non-inferior after IVL (mean: 6.10 mm2 , 95% confidence interval [95% CI]: 5.32-6.87 mm2 ) versus RA (6.60 mm2 , 95% CI: 5.66-7.54 mm2 ; difference in MSA: -0.50 mm2 , 95% CI: -1.52-0.52 mm2 ; non-inferiority margin: -1.60 mm2 ). Stent expansion was similar (RA: 0.83 ± 0.10 vs. IVL: 0.82 ± 0.11; p = 0.79). There were no significant differences regarding contrast media consumption (RA: 183.1 ± 68.8 vs. IVL: 163.3 ± 55.0 mL; p = 0.47), radiation dose (RA: 7269 ± 11288 vs. IVL: 5010 ± 4140 cGy cm2 ; p = 0.68), and procedure time (RA: 79.5 ± 34.5 vs. IVL: 66.0 ± 19.4 min; p = 0.18). CONCLUSION: IVL is non-inferior regarding MSA and results in a similar stent expansion in a random comparison with RA. Procedure time, contrast volume, and dose-area product do not differ significantly.

Reduction of arterial stiffness in depressive individuals responding to multimodal treatment.

BACKGROUND: Depressive individuals are at higher risk for cardiovascular diseases (CVD). Thus, cardiovascular parameters such as arterial stiffness, often measured by pulse wave velocity (PWV), should be monitored. Recent research indicated that depressive individuals exhibit higher PWV, but there is little data on the changeability of PWV through multimodal treatment. This study investigated PWV in moderately to severe depressive individuals before and after undergoing treatment in dependence on responding or not responding to treatment. METHODS: 47 participants (31 females, 16 males) underwent a PWV measurement and filled out a questionnaire surveying depressive symptom severity before and after a six-week psychiatric rehabilitation treatment including multimodal interventions. Subjects were divided in responders and non-responders, depending on their treatment success. RESULTS: A mixed ANCOVA analysis indicated no significant main effect of responder status, but a significant main effect of measurement time and a significant interaction between responder status and measurement time. Responders exhibited a significant decrease in PWV across time, while no significant change in PWV across time was found for non-responders. LIMITATIONS: Results are limited by the lack of a control group. The influence of medication duration or medication type was not considered in the analyses. Causality of the relationship between PWV and depression cannot be determined. CONCLUSION: These findings show that PWV can be positively modified in depressive individuals responding to treatment. This effect cannot solely be attributed to pharmacological interventions but rather the combination of multimodal interventions, thus highlighting the clinical relevance of multimodal treatment in depression and comorbid disorders.

Gene expression analysis of MAOA and the clock gene ARNTL in individuals with bipolar disorder compared to healthy controls.

INTRODUCTION: Circadian rhythms are associated with bipolar disorder (BD). This cross-sectional study aimed at investigating ARNTL and MAOA gene expression differences (1) between individuals with BD and controls, (2) between affective episodes, and (3) the relationship between ARNTL and MAOA expression. METHODS: ARNTL and MAOA gene expression in peripheral mononuclear blood cells were analysed from fasting blood samples (BD n = 81, controls n = 54) with quantitative real-time PCR operating on TaqMan® assays (normalised to 18S RNA expression). ANCOVAs corrected for age, sex, body mass index, and medication was used to evaluate expression differences and correlation analyses for the relation between ARNTL and MAOA expression. RESULTS: ARNTL gene expression differed between affective episodes (F(2,78) = 3.198, p = 0.047, Partial Eta2= 0.083), but not between BD and controls (n.s.). ARNTL and MAOA expression correlated positively in BD (r = 0.704, p < 0.001) and in controls (r = 0.932, p < 0.001). MAOA expression differed neither between BD and controls nor between affective episodes (n.s.). DISCUSSION: Clock gene expression changes were observed in different affective states of BD. More precisely, ARNTL gene expression was significantly higher in euthymia than in depression. ARNTL and MAOA gene expression correlated significantly in BD and in controls, which emphasises the strong concatenation between circadian rhythms and neurotransmitter breakdown.

Sex differences in zonulin in affective disorders and associations with current mood symptoms.

INTRODUCTION: The bidirectional connection between the brain and the gut within psychiatric entities has gained increasing scientific attention over the last years. As a regulator of intestinal permeability, zonulin acts as a key player on the interface of this interplay. Like several psychiatric disorders, intestinal permeability was associated with inflammation in previous findings. METHODS: In this study we explored differences in zonulin serum levels in currently depressed (n = 55) versus currently euthymic (n = 37) individuals with an affective disorder. Further, we explored sex differences and possible influences on zonulin and affective symptoms like medication, age, body mass index, and smoking status. RESULTS: Serum zonulin was significantly higher in females than in men independent from affective status (z = -2.412, p = .016). More specifically, females in the euthymic subgroup had higher zonulin levels than euthymic men (z = -2.114, p = .035). There was no difference in zonulin serum levels in individuals taking or not taking a specific psychopharmacotherapy. We found no correlation between zonulin serum levels and depression severity. DISCUSSION: Increased serum zonulin levels as a proxy for increased intestinal permeability in women may indicate a state of elevated susceptibility for depression-inducing stimuli.

The association between anti-inflammatory effects of long-term lithium treatment and illness course in Bipolar Disorder.

INTRODUCTION: Altered levels of acute-phase proteins are often described in different conditions in BD. Nevertheless, data on the association between lithium treatment and inflammatory markers in the long-term course of BD are still missing. The aim of the study was to examine the long-term course of BD concerning long-term lithium treatment, chronic inflammatory processes and symptom progression. Furthermore, the association between duration of lithium treatment and levels of hsCRP was explored. METHODS: 267 individuals (males= 139, females= 128) with BD were included. Duration of lithium treatment as well as symptom progression, defined as the increase in severity of symptoms, number of episodes a year and duration of episodes within a period of 1.5 years in the past and hsCRP were evaluated. RESULTS: Male individuals with symptom progression over time had significantly lower duration of lithium treatment compared to individuals without symptoms progression (U= 47.4, p=.037). There were significantly higher levels of hsCRP in male individuals with symptom progression compared to males without symptom progression (U= 47.5, p=.027). Further, there was a significant negative correlation between the duration of lithium treatment and hsCRP levels in the whole sample (r= -.276, p<.05). CONCLUSION: Our results show that an altered inflammatory state may be associated with a more severe illness course in BD. Further, a longer duration of lithium treatment may be associated with lower symptom progression. The shown association between hsCRP-levels and lithium treatment duration suggests a potential anti-inflammatory effect of lithium as a mediator of its significant positive outcome effect in BD.

Instant rule-out of suspected non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin T with Copeptin versus a single low high-sensitivity cardiac troponin T: findings from a large pooled individual data analysis on 10,329 patients.

BACKGROUND: Evidence is sparse and inconsistent on the role of a dual marker strategy (DMS) combining Copeptin with cardiac troponin T (cTnT) for instant rule-out of a non-ST-segment myocardial infarction (NSTEMI) when high sensitivity cardiac troponin T (hs-cTnT) is used. METHODS: Data on 10,329 patients from 5 trials were pooled to evaluate initial Copeptin in combination with hs-cTnT against a single marker strategy (SMS) based on hs-cTnT < limit of detection. Endpoints were sensitivities and negative predictive values (NPV) for rule-out of NSTEMI, 30-day all-cause mortality and rates of applicability for DMS or SMS. RESULTS: NPV for rule-out of NSTEMI was high, exceeding 99.0% for the lower limits of the 95% confidence intervals (99.0% vs 99.2%) for DMS and SMS, and NPV for all cause death at 30 days was similar with very low mortality after rule-out [0.07% (0.0-0.4%) vs 0.0% (0.0-1.2%), p = 1.0], but applicability was 2.4-fold higher [64.6% (63.0-66.2%) vs 27.9% (26.2%-29.7%), p < 0.001] with DMS than SMS. In a secondary analysis on DMS after inclusion of high risk patients, performance and applicability were similar. CONCLUSION: Findings corroborate the 2015 European Society of Cardiology recommendation to use dual marker strategy for instant rule-out of NSTEMI, extending evidence to hs-cTnT. Novel data demonstrate a comparably safe and effective instant rule-out with Copeptin in combination with hs-cTnT versus a single marker strategy based on very low hs-cTnT but a more than twofold higher applicability of the dual marker strategy without the need to exclude very early presenters or other important subgroups. Dual marker strategy using hs-cTnT at 99th percentile and Copeptin versus ESC 0-h immediate rule-out based on hs-cTnT < limit of detection.

A comprehensive diagnostic approach combining phylogenetic disease bracketing and CT imaging reveals osteomyelitis in a Tyrannosaurus rex.

Traditional palaeontological techniques of disease characterisation are limited to the analysis of osseous fossils, requiring several lines of evidence to support diagnoses. This study presents a novel stepwise concept for comprehensive diagnosis of pathologies in fossils by computed tomography imaging for morphological assessment combined with likelihood estimation based on systematic phylogenetic disease bracketing. This approach was applied to characterise pathologies of the left fibula and fused caudal vertebrae of the non-avian dinosaur Tyrannosaurus rex. Initial morphological assessment narrowed the differential diagnosis to neoplasia or infection. Subsequent data review from phylogenetically closely related species at the clade level revealed neoplasia rates as low as 3.1% and 1.8%, while infectious-disease rates were 32.0% and 53.9% in extant dinosaurs (birds) and non-avian reptiles, respectively. Furthermore, the survey of literature revealed that within the phylogenetic disease bracket the oldest case of bone infection (osteomyelitis) was identified in the mandible of a 275-million-year-old captorhinid eureptile Labidosaurus. These findings demonstrate low probability of a neoplastic aetiology of the examined pathologies in the Tyrannosaurus rex and in turn, suggest that they correspond to multiple foci of osteomyelitis.

Transcatheter aortic valve implantation in nonagenarians: insights from the German Aortic Valve Registry (GARY).

OBJECTIVE: The aim of this study was to compare the outcome of nonagenarians (≥ 90 years) with that of younger (< 90 years) patients undergoing transcatheter aortic valve implantation (TAVI) in current practice. METHODS: Data are collected from the German Aortic Valve Registry (GARY), which was designed to evaluate current practice in the invasive treatment of patients with aortic valve diseases in Germany. Data were analyzed regarding procedural outcome, 30-day, and 1-year outcomes of nonagenarians in comparison to that of younger patients. RESULTS: Between 2011 and 2015, 2436/33,051 (7.3%) nonagenarians underwent TAVI and were included in GARY. Nonagenarians were significantly more often male (45.2% vs. 40.0%, p < 0.001), frail (38.7% vs. 34.7%, p < 0.001), and had higher EuroSCORE scores than younger patient group (23.2% vs. 17.0%). Nonagenarians were significantly less often treated via transapical access (16.3% vs. 22.3%, p < 0.001). Procedure was performed significantly less often in general anesthesia (58.2% vs. 60.7%, p = 0.02) in nonagenarians, while necessity of pacemaker implantation was significantly higher in nonagenarians (27.2% vs. 24.8%, p > 0.001). The incidence of other typical postprocedural complications such as severe bleeding events and vascular complications were comparable between groups. However, 30-day (5.2% vs. 3.9%) and 1-year (22.7% vs. 17.7%) mortality rates were significantly higher among nonagenarians and age ≥ 90 years could be identified as an isolated risk factor for mortality. CONCLUSION: TAVI is a highly standardized procedure that can be performed safely with high procedural success even in very old patients. Although mortality is significantly higher in these patients-most probably due to the intrinsic higher risk profile of the very old patients-the results are still acceptable. To optimize outcome, especially elderly patients seem to profit from a procedure under local anesthesia or conscious sedation, to minimize the rate of postoperative delirium and the length of stay and to facilitate early mobilization.

Everolimus- vs. novolimus-eluting bioresorbable scaffolds in patients with acute coronary syndrome.

BACKGROUND: Limited data exist on bioresorbable scaffolds (BRS) in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate novolimus-eluting BRS (DESolve) as interventional treatment for patients with ACS, and to compare its 12-month outcomes with the everolimus-eluting bioresorbable scaffolds (Absorb). METHODS: In this retrospective study, patients with ACS (including unstable angina pectoris, ST-segment elevation myocardial infarction, or non-ST-segment elevation myocardial infarction) treated with either the Absorb or the DESolve BRS were evaluated in a 1:1 matched-pair analysis. Major adverse cardiac events (MACE), including death, myocardial infarction, and target lesion revascularization, were evaluated as a major endpoint. The occurrence of scaffold thrombosis was also assessed. RESULTS: A total of 102 patients were eligible for this analysis. The rate of MACE at 12 months was comparable between the Absorb and the DESolve group (8.3% vs. 6.8%, p = 0.738). The occurrence of target lesion revascularization (6.2% vs. 4.7%; p = 0.700) and scaffold thrombosis (4.1% vs. 2.1%; p = 0.580) was comparable as well. All instances of scaffold thrombosis occurred within 30 days of the index procedure. CONCLUSION: In this study, similar 12-month event rates were observed for both BRS types after implantation for the treatment of ACS.

[Prehospital management of acute coronary syndrome in patients on long-term direct oral anticoagulant treatment]. / Prähospitale Behandlung des akuten Koronarsyndroms unter DOAK-Dauertherapie.

BACKGROUND: Despite an increasing incidence of patients suffering from acute coronary syndrome (ACS) under simultaneous treatment with direct oral anticoagulants (DOAC), neither sufficient scientific data nor uniform guidelines for the anticoagulation treatment of these patients are currently available. OBJECTIVE: The aim of this study was to determine the current practice of preclinical treatment of ACS in patients under DOAC treatment. MATERIAL AND METHODS: An internet and paper-based survey of emergency physicians, specialists of internal medicine, anesthesiologists, emergency and intensive care physicians was performed concerning the prehospital treatment of ACS in patients under long-term DOAC treatment. RESULTS: Overall, 284 questionnaires were answered. Substantial differences in the current treatment of ACS under long-term DOAC therapy were identified. While 39% of the respondents stated that they administer a combination treatment of heparin and acetylsalicylic acid (ASA), 36% renounced the administration of heparin. If a dose reduction was performed, 71% answered that they reduce the heparin dosage. Also, in cases of ST-segment elevation myocardial infarction 48% of the physicians renounced the administration of heparin. CONCLUSION: In Germany there is currently a heterogeneous practice of emergency treatment of ACS patients under DOAC therapy with respect to the administration of heparin and ASA. Therefore, guidelines of the specialist medical societies should address the prehospital emergency anticoagulation management of ACS in patients under therapy with DOAC, which correspond to the needs of patients and emergency physicians.

A phase II randomized clinical trial of the effect of metformin versus placebo on progression-free survival in women with metastatic breast cancer receiving standard chemotherapy.

OBJECTIVES: Pre-clinical data suggest metformin might enhance the effect of chemotherapy in breast cancer (BC). We conducted a Phase II randomized trial of chemotherapy plus metformin versus placebo in metastatic breast cancer (MBC). MATERIAL AND METHODS: In this double blind phase II trial we randomly assigned non-diabetic MBC patients on 1st to 4th line chemotherapy to receive metformin 850 mg po bid or placebo bid. Primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), response rate (RR), toxicity and quality of life (QOL). With 40 subjects and a type-one error of 0.2 (one-sided), a PFS hazard ratio (HR) of 0.58 could be detected with 80% power. RESULTS: 40 patients were randomized (22 metformin, 18 placebo) with a mean age of 55 vs 57 years and ER/PR positive BC in 86.4% vs 83.3% off metformin vs placebo, respectively. Mean BMI was 27kg/m2 in both arms. The majority of patients were on 1st line chemotherapy. Grade 3-4 toxicity occurred in 31.8% (metformin) vs 58.8% (placebo). Best response: Partial response 18.2% metformin vs 25% placebo, stable disease 36.4% metformin vs 18.8% placebo, progressive disease 45.4% metformin vs 56.2% placebo. Mean PFS was 5.4 vs 6.3 months (metformin vs placebo), HR 1.2 (95% CI 0.63-2.31). Mean OS was 20.2 (metformin) vs 24.2 months (placebo), HR 1.68 (95% CI 0.79-3.55). CONCLUSION: In this population metformin showed no significant effect on RR, PFS or OS. These results do not support the use of metformin with chemotherapy in non-diabetic MBC patients.

The relationship between "Eyes Reading" ability and verbal memory in bipolar disorder.

In psychiatric disorders, neurocognitive impairments are prevalent and have been associated with poor outcome. Deficits in Theory of Mind (ToM, "mentalising") have also been observed in bipolar disorder (BD); however, the literature shows inconsistent data. The aim of this study was to explore ToM performance in a well-characterized sample of euthymic individuals with BD and its relationship with neurocognitive function. One hundred sixteen euthymic patients with BD between 18 and 74 years (mean age = 42.4, SD = 13.8) and 79 healthy controls (mean age = 39.8, SD = 16.5) were investigated with an extensive neurocognitive test battery (Trail Making Test A/B, d2 Test of Attention, Stroop Color-Word Test, California Verbal Learning Test, Multiple Choice Vocabulary Test). Additionally, all participants were given the Reading the Mind in the Eyes Test (RMET) to measure affective ToM, the ability to make assumptions about other people´s feelings. Overall, "Eyes Reading" performance was not impaired in individuals with BD compared with controls. However, a significant relationship between RMET and verbal memory in BD was shown, particularly in males. Data showed worse RMET performance in patients with memory deficits compared to patients without memory deficits and controls. Due to cross-sectional data, no conclusions can be made with respect to cause and effect.

[Heart valve disesases : How sufficient is the knowledge of the German population?] / Herzklappenerkrankungen : Wie aufgeklärt ist die deutsche Bevölkerung?

To evaluate the awareness and knowledge of the German population regarding diseases in general, a survey of 1446 people aged 60 years or older was conducted in 14 German towns. The focus was on heart valve diseases with special emphasis on aortic valve stenosis (AS). While cancer was the disease that respondents were most concerned about (25.2%), only 3.3% were concerned about heart valve diseases. In this respect, the knowledge was broadly limited: only 7.4% of participants claimed to have some familiarity with heart valve diseases and only 12.5% could correctly describe the symptoms of AS. Even so, 35.0% of the participants could correctly name the number of human heart valves, 71.6% knew at least one therapy option for AS and 30.6% were familiar with transcatheter aortic valve implantation (TAVI). After providing a brief clarification of the prevalence, symptoms and course of AS, 45.6% of respondents were more concerned about the condition, 15.7% wanted to know more about the symptoms of AS and 4.7% even recognized the typical symptoms in themselves. Most of the participants would like to seek more information preferably in discussion with a specialist physician (77.2%), with their general practitioner (43.2%) or using the internet (29.7%). Despite its high prevalence, high morbidity and mortality, the vast majority of the German population were neither concerned nor fully aware of treatment options for AS. There is a strong case for public awareness campaigns that provide better knowledge of AS, and support check-ups that enable timely treatment and the avoidance of unnecessary hospitalization and death.

Correlation of native T1 mapping with right ventricular function and pulmonary haemodynamics in patients with chronic thromboembolic pulmonary hypertension before and after balloon pulmonary angioplasty.

OBJECTIVES: The aim of this study was to assess native T1 mapping in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) before and 6 months after balloon pulmonary angioplasty (BPA) and compare the results with right heart function and pulmonary haemodynamics. METHODS: Magnetic resonance imaging at 1.5 T and right heart catheterisation were performed in 21 consecutive inoperable CTEPH patients before and 6 months after BPA. T1 values were measured within the septal myocardium, the upper and lower right ventricular insertion points, and the lateral wall at the basal short-axis section. In addition, the area-adjusted septal native T1 time (AA-T1) was calculated and compared with right ventricular function (RVEF), mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). RESULTS: The mean AA-T1 value decreased significantly after BPA (1,045.8 ± 44.3 ms to 1,012.5 ± 50.4 ms; p < 0.001). Before BPA, native T1 values showed a moderate negative correlation with RVEF (r = -0.61; p = 0.0036) and moderate positive correlations with mPAP (r = 0.59; p < 0.01) and PVR (r = 0.53; p < 0.05); after BPA correlation trends were present (r = -0.21, r = 0.30 and r = 0.35, respectively). CONCLUSIONS: Native T1 values in patients with inoperable CTEPH were significantly lower after BPA and showed significant correlations with RVEF and pulmonary haemodynamics before BPA. Native T1 mapping seems to be indicative of reverse myocardial tissue remodelling after BPA and might therefore have good potential for pre-procedural patient selection, non-invasive therapy monitoring and establishing a prognosis. KEY POINTS: • BPA is a promising treatment option for patients with inoperable CTEPH • Native septal T1 values significantly decrease after BPA and show good correlations with right ventricular function and haemodynamics before BPA • Prognosis and non-invasive therapy monitoring might be supported in the future by native T1 mapping.

Epigenetics of the molecular clock and bacterial diversity in bipolar disorder.

Objectives The gut microbiome harbors substantially more genetic material than our body cells and has an impact on a huge variety of physiological mechanisms including the production of neurotransmitters and the interaction with brain functions through the gut-brain-axis. Products of microbiota can affect methylation according to preclinical studies. The current investigation aimed at analyzing the correlation between gut microbiome diversity and the methylation of the clock gene ARNTL in individuals with Bipolar Disorder (BD). Methods Genomic DNA was isolated from fasting blood of study participants with BD (n = 32). The methylation analysis of the ARNTL CG site cg05733463 was performed by bisulfite treatment of genomic DNA with the Epitect kit, PCR and pyrosequencing. Additionally, DNA was extracted from stool samples and subjected to 16S rRNA sequencing. QIIME was used to analyze microbiome data. Results Methylation status of the ARNTL CpG position cg05733463 correlated significantly with bacterial diversity (Simpson index: r= -0.389, p = 0.0238) and evenness (Simpson evenness index: r= -0.358, p = 0.044). Furthermore, bacterial diversity differed significantly between euthymia and depression (F(1,30) = 4.695, p = 0.039). Discussion The results of our pilot study show that bacterial diversity differs between euthymia and depression. Interestingly, gut microbiome diversity and evenness correlate negatively with methylation of ARNTL, which is known to regulate monoamine oxidase A transcription. We propose that alterations in overall diversity of the gut microbiome represent an internal environmental factor that has an epigenetic impact on the clock gene ARNTL which is thought to be involved in BD pathogenesis.

[MINOCA-myocardial infarction with non-obstructive coronary arteries]. / MINOCA ­ Myokardinfarkt ohne obstruktive Koronarerkrankung.

In recent years it has been observed with increasing interest that there is a group of patients with electrocardiographic and laboratory features of myocardial infarction (MI) but no obstructive coronary artery disease (<50% diameter stenosis). For this entity the term myocardial infarction with non-obstructive coronary arteries (MINOCA) has been coined. The prevalence of MINOCA is estimated to be 6-9% among patients diagnosed with MI and it is more common in women than men as well as in patients presenting with NSTEMI than in those presenting with STEMI. The MINOCA is a working diagnosis that requires a further diagnostic work-up by invasive techniques, such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) or non-invasive imaging with cardiac magnetic resonance imaging (CMRI). When it is ascertained that obstructive coronary artery disease has not been inadvertently overlooked, other coronary disorders, such as plaque rupture or erosion, thrombosis, dissection, spasms or microvascular dysfunction should be evaluated. Furthermore, myocarditis or tako-tsubo cardiomyopathy should be excluded by CMRI as non-coronary causes. The further treatment and prognosis of patients with MINOCA depend on the underlying cause and the final diagnosis.

Leadless pacing.

Leadless self-contained intracardiac pacemakers were developed with the aim of abolishing the short- and long-term risk of lead- and pocket-related complications associated with transvenous devices. Leadless pacemakers promise minimally invasive procedures, long battery lives, and small amounts of foreign materials in the body. Experiences with the pioneering single-chamber devices have provided reasons for optimism about the future of the leadless concept. In the future, as more patients receive and live longer with implantable devices, the total risk of procedure- and lead-related complications is expected to increase, adding a sense of urgency to the need for leadless alternatives to transvenous pacemakers. This review surveys the performance of currently available leadless pacemakers as well as emerging new innovative adaptations and applications of the leadless concept.

[Patent foramen ovale-intervention or pharmaceutical treatment]. / Persistierendes Foramen ovale ­ Intervention oder Arzneitherapie.

BACKGROUND: Approximately 40-50% of patients with cryptogenic stroke have a patent foramen ovale (PFO). A concomitant atrial septal aneurysm aggravates the risk of recurrent stroke. OBJECTIVE: The most important changes regarding the evidence for interventional closure of a PFO in patients with cryptogenic stroke are described. This includes the prerequisites for making a diagnosis and the indications for interventional treatment. The article also provides an overview about platelet aggregation inhibitor treatment with and without oral anticoagulation. CURRENT DATA: The balance between benefits and risks of interventional versus pharmaceutical treatment in patients with cryptogenic stroke and PFO has so far not been sufficiently proven. In 2017 two prospective randomized trials (CLOSE and REDUCE) and the long-term follow-up results of the RESPECT study were published, followed by the results of the DEFENSE-PFO study in 2018. A better assessment of the weighing up of the treatment options can now be made. All four studies showed that the interventional treatment of PFO is superior to pharmaceutical treatment alone for patients with cryptogenic stroke under 60 years of age. CONCLUSION: There was a significant reduction in the incidence of recurrent stroke in patients with interventional PFO closure compared with pharmaceutical treatment. The complication rate of PFO closure is very low and younger patients (<60 years) in particular benefit from PFO closure.

Early changes in N-terminal pro-B-type natriuretic peptide levels after transcatheter aortic valve replacement and its impact on long-term mortality.

BACKGROUND: N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) levels correlate with higher peri-procedural mortality after transcatheter aortic valve replacement (TAVR). The long-term prognostic value of NT-proBNP within the first days after TAVR, however, remains unclear. This study examined early changes in NT-proBNP prior to and within 6 days after TAVR, the diagnostic value of this biomarker regarding aortic regurgitation (AR), and its prognostic value regarding one-year mortality. METHODS AND RESULTS: NT-proBNP concentrations were measured in 504 consecutive patients undergoing transapical (TA) or transfemoral (TF) TAVR before and directly after TAVR as well as 4 h and 1, 2, 3, and 6 days after TAVR. The follow-up period was 1 year. NT-proBNP was elevated in all patients at baseline (median 2141 ng/L [IQR 1021-5319 ng/L]). NT-proBNP changes in the first 6 days after TAVR showed significant differences depending on the approach, with a greater and more prolonged rise evident in TA-TAVR patients. NT-proBNP was an independent predictor of mortality in TA patients with AR, with an AUC of 0.794 (95% CI 0.663-0.925; P = 0.003) when measured on day 3 after TAVR. For TF patients with AR and reduced left ventricular systolic function, the AUC for prediction of mortality was 0.897 (95% CI 0.778-1.0; P = 0.004) on day 2. CONCLUSIONS: The prognostic information of early post-procedural NT-proBNP concentrations is superior to pre-procedural values regarding all-cause mortality within 1 year. Post-procedural NT-proBNP must be interpreted in relation to the TAVR approach. NT-proBNP predicts mortality in TF-TAVR patients with AR and reduced left ventricular function.