Platelet mass cytometry reveals dysregulation of prothrombotic pathways in essential thrombocythemia.

Thromboembolic events are common in patients with essential thrombocythemia (ET). However, the pathophysiological mechanisms underlying the increased thrombotic risk remain to be determined. Here, we perform the first phenotypical characterization of platelet expression using single-cell mass cytometry in six ET patients and six age- and sex-matched healthy individuals. A large panel of 18 transmembrane regulators of platelet function and activation were analyzed, at baseline and after ex-vivo stimulation with thrombin receptor-activating peptide (TRAP). We detected a significant overexpression of the activation marker CD62P (p-Selectin) (p = .049) and the collagen receptor GPVI (p = .044) in non-stimulated ET platelets. In contrast, ET platelets had a lower expression of the integrin subunits of the fibrinogen receptor GPIIb/IIIa CD41 (p = .036) and CD61 (p = .044) and of the von Willebrand factor receptor CD42b (p = .044). Using the FlowSOM algorithm, we identified 2 subclusters of ET platelets with a prothrombotic expression profile, one of them (cluster 3) significantly overrepresented in ET (22.13% of the total platelets in ET, 2.94% in controls, p = .035). Platelet counts were significantly increased in ET compared to controls (p = .0123). In ET, MPV inversely correlated with platelet count (r=-0.96). These data highlight the prothrombotic phenotype of ET and postulate GPVI as a potential target to prevent thrombosis in these patients.

Essential thrombocythemia (ET) is a rare disease characterized by an increased number of platelets in the blood. As a complication, many of these patients develop a blood clot, which can be life-threatening. So far, the reason behind the higher risk of blood clots is unclear. In this study, we analyzed platelet surface markers that play a critical role in platelet function and platelet activation using a modern technology called mass cytometry. For this purpose, blood samples from 6 patients with ET and 6 healthy control individuals were analyzed. We found significant differences between ET platelets and healthy platelets. ET platelets had higher expression levels of p-Selectin (CD62P), a key marker of platelet activation, and of the collagen receptor GPVI, which is important for clot formation. These results may be driven by a specific platelet subcluster overrepresented in ET. Other surface markers, such as the fibrinogen receptor GPIIb/IIIa CD41, CD61, and the von Willebrand factor receptor CD42b, were lower expressed in ET platelets. When ET platelets were treated with the clotting factor thrombin (thrombin receptor-activating peptide, TRAP), we found a differential response in platelet activation compared to healthy platelets. In conclusion, our results show an increased activation and clotting potential of ET platelets. The platelet surface protein GPVI may be a potential drug target to prevent abnormal blood clotting in ET patients.

Increase of Cardiac Autoantibodies Against Beta-2-adrenergic Receptor During Acute Cellular Heart Transplant Rejection.

BACKGROUND: Acute cellular rejection (ACR) in heart transplant (HTx) recipients may be accompanied by cardiac cell damage with subsequent exposure to cardiac autoantigens and the production of cardiac autoantibodies (aABs). This study aimed to evaluate a peptide array screening approach for cardiac aABs in HTx recipients during ACR (ACR-HTx). METHODS: In this retrospective single-center observational study, sera from 37 HTx recipients, as well as age and sex-matched healthy subjects were screened for a total of 130 cardiac aABs of partially overlapping peptide sequences directed against structural proteins using a peptide array approach. RESULTS: In ACR-HTx, troponin I (TnI) serum levels were found to be elevated. Here, we could identify aABs against beta-2-adrenergic receptor (ß-2AR: EAINCYANETCCDFFTNQAY) to be upregulated in ACR-HTx (intensities: 0.80 versus 1.31, P = 0.0413). Likewise, patients positive for ß-2AR aABs showed higher TnI serum levels during ACR compared with aAB negative patients (10.0 versus 30.0 ng/L, P = 0.0375). Surprisingly, aABs against a sequence of troponin I (TnI: QKIFDLRGKFKRPTLRRV) were found to be downregulated in ACR-HTx (intensities: 3.49 versus 1.13, P = 0.0025). A comparison in healthy subjects showed the same TnI sequence to be upregulated in non-ACR-HTx (intensities: 2.19 versus 3.49, P = 0.0205), whereas the majority of aABs were suppressed in non-ACR-HTx. CONCLUSIONS: Our study served as a feasibility analysis for a peptide array screening approach in HTx recipients during ACR and identified 2 different regulated aABs in ACR-HTx. Hence, further multicenter studies are needed to evaluate the prognostic implications of aAB testing and diagnostic or therapeutic consequences.

Depression mediates the association between health literacy and health-related quality of life after myocardial infarction.

Introduction: So far, health literacy (HL) and its related factors in patients with acute myocardial infarction received little attention. Thus, the objective of this study was to investigate the associations between the different dimensions of HL and disease-specific health-related quality of life (HRQOL), and factors that may affect these relations in patients after acute myocardial infarction (AMI). Methods: All survivors of AMI between June 2020 and September 2021, from the Myocardial Infarction Registry Augsburg (n=882) received a postal questionnaire on HL [Health Literacy Questionnaire (HLQ)], HRQOL (MacNew Heart Disease HRQOL questionnaire) and depression (Patient Health Questionnaire). From the 592 respondents, 546 could be included in the analysis. Multivariable linear regression models were performed to investigate the associations between the nine subscales of the HLQ and the total score and three subscales of the MacNew questionnaire. A mediation analysis was performed to estimate direct and indirect effects of HL on HRQOL taking into account the mediating effect of depression. Results: In the sample of 546 patients (72.5% male, mean age 68.5 ± 12.2 years), patients with poor education showed significantly lower HLQ scores. Significant associations between the subscales of the HLQ and the MacNew were found, which remained significant after adjustment for sociodemographic variables with few exceptions. More than 50% of the association between HL and HRQOL was mediated by depression in seven HLQ subscales and a complete mediating effect was found for the HLQ subscales 'Actively managing my health' and 'Appraisal of health information'. Discussion: Depression mediates the associations between HL and disease-specific HRQOL in patients with myocardial infarction.

Association Between Acute Myocardial Infarction Symptoms and Short- and Long-term Mortality After the Event.

BACKGROUND: In this study, we investigated various acute myocardial infarction (AMI) symptoms and their associations with short-term (28 day) and long-term mortality. METHODS: The analysis was based on 5900 patients, aged 25 to 84 years, with first-time AMI recorded by the population-based Myocardial Infarction Registry Augsburg between 2010 and 2017. Median follow-up time was 3.8 years (interquartile range: 1.1-6.3). As part of a face-to-face interview, the presence (yes/no) of 11 most common AMI symptoms at the acute event was assessed. Using multivariable-adjusted logistic regression and Cox regression models, the association between various symptoms and all-cause mortality was investigated. P values of the regression models were false discovery rate adjusted. RESULTS: Pain in various body parts (chest pain, left and right shoulder/arm/hand, between shoulder blades), sweating, nausea/vomiting, dizziness and fear of death/feeling of annihilation were significantly associated with a decreased 28-day mortality after AMI. The pain symptoms and sweating were also significantly associated with a decreased long-term mortality. Shortness of breath was significantly associated with a higher long-term mortality. CONCLUSIONS: The absence of several symptoms, including typical chest discomfort (chest pain or retrosternal pressure/tightness), is associated with unfavourable outcomes after AMI. This finding has implications for patient management and public health measures designed to encourage appropriate and prompt medical consultation of patients with atypical AMI symptoms.

Virtual non-contrast series of photon-counting detector computed tomography angiography for aortic valve calcium scoring.

The aim of our study was to evaluate two different virtual non-contrast (VNC) algorithms applied to photon counting detector (PCD)-CT data in terms of noise, effectiveness of contrast media subtraction and aortic valve calcium (AVC) scoring compared to reference true non-contrast (TNC)-based results. Consecutive patients underwent TAVR planning examination comprising a TNC scan, followed by a CTA of the heart. VNC series were reconstructed using a conventional (VNCconv) and a calcium-preserving (VNCpc) algorithm. Noise was analyzed by means of the standard deviation of CT-values within the left ventricle. To assess the effectiveness of contrast media removal, heart volumes were segmented and the proportion of their histograms > 130HU was taken. AVC was measured by Agatston and volume score. 41 patients were included. Comparable noise levels to TNC were achieved with all VNC reconstructions. Contrast media was effectively virtually removed (proportions > 130HU from 81% to < 1%). Median calcium scores derived from VNCconv underestimated TNC-based scores (up to 74%). Results with smallest absolute difference to TNC were obtained with VNCpc reconstructions (0.4 mm, Br36, QIR 4), but with persistent significant underestimation (median 29%). Both VNC algorithms showed near-perfect (r²>0.9) correlation with TNC. Thin-slice VNC reconstructions provide equivalent noise levels to standard thick-slice TNC series and effective virtual removal of iodinated contrast. AVC scoring was feasible on both VNC series, showing near-perfect correlation, but with significant underestimation. VNCpc with 0.4 mm slices and Br36 kernel at QIR 4 gave the most comparable results and, with further advances, could be a promising replacement for additional TNC.

Do patients with diabetes with new onset acute myocardial infarction present with different symptoms than non-diabetic patients?

Background: The objective of this study was to investigate the differences in presenting symptoms between patients with and without diabetes being diagnosed with an acute myocardial infarction (AMI). Methods: A total of 5,900 patients with a first-time AMI were included into the analysis. All patients aged between 25 and 84 years were recorded by the population-based Myocardial Infarction Registry in Augsburg, Germany, between 2010 and 2017. The presence (yes/no) of 12 AMI typical symptoms during the acute event was assessed within the scope of a face-to-face interview. Multivariable adjusted logistic regression models were calculated to analyze the associations between presenting symptoms and diabetes mellitus in AMI patients. Results: Patients with diabetes had significantly less frequent typical pain symptoms, including typical chest pain. Also, other symptoms like sweating, vomiting/nausea, dizziness/vertigo and fear of death/feeling of annihilation occurred significantly more likely in non-diabetic patients. The only exception was the symptom of shortness of breath, which was found significantly more often in patients with diabetes. In multivariable-adjusted regression models, however, the observed effects were attenuated. In patients younger than 55 years, the associations between diabetes and various symptoms were mainly missing. Conclusions: Type 2 diabetes mellitus is a risk factor not only for the development of AMI, but is also associated with an adverse outcome after AMI. Atypical clinical presentation additionally complicates the diagnostic process. It is therefore essential for physicians to be aware of the more often atypical symptoms that diabetic AMI patients report.

Reticulated Platelets Predict Cardiovascular Death and Adverse Events in Coronary Artery Disease: A Systematic Review and Meta-analysis.

BACKGROUND: The pro-thrombotic immature or reticulated platelets (RPs) are known to be elevated in high-risk patients and in different pathological settings. It has been shown that RPs correlate with an insufficient antiplatelet response to antiplatelet agents. RPs are emerging novel predictors of adverse cardiovascular events in cardiovascular disease. This study, using the totality of existing evidence, evaluated the prognostic role of RPs in patients with coronary artery disease. METHODS: We performed a systematic review and meta-analysis including trials of acute and chronic coronary syndrome reporting clinical outcomes according to RPs levels in the peripheral blood. We compared patients with elevated RPs (RPshigh) to patients without elevated RPs (RPslow). Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints were cardiovascular death, myocardial infarction, ischemic stroke, urgent coronary revascularization and bleedings. RESULTS: A total of 7 studies, including 2213 patients, were included. The risk for MACCE was significantly higher in RPshigh compared to RPslow patients (OR 2.67 [1.87; 3.81], I2 = 43.8%). RPshigh were associated with cardiovascular death (OR 2.09 [1.36; 3.22], I2 = 40.4%). No associations for RPshigh were detected with the other singular components of MACCE: myocardial infarction (OR 1.73 [0.89; 3.38] I2 = 60.5%) and stroke (OR 1.72 [0.59; 4.96] I2 = 21%). The risk of bleeding did not differ between groups(OR 0.58 [0.15; 2.22] I2 = 86.1%). CONCLUSION: Elevated RPs are significantly associated with increased risk of cardiovascular events and cardiovascular death.

Fatigue, Depression and Health-Related Quality of Life in Patients with Post-Myocardial Infarction during the COVID-19 Pandemic: Results from the Augsburg Myocardial Infarction Registry.

The interplay between fatigue and depression and their association with health-related quality of life (HRQoL) after acute myocardial infarction (AMI) has received little attention during the COVID-19 pandemic. Therefore, this study evaluated the frequency of fatigue and depression in post-AMI patients during the COVID-19 pandemic and investigated the cross-sectional associations between fatigue, depression and HRQoL. METHODS: The analysis was based on population-based Myocardial Infarction Registry Augsburg data. All survivors of AMI between 1 June 2020 and 15 September 2021 were included (n = 882) and received a postal questionnaire containing questions about fatigue (Fatigue Assessment Scale), depression (Patient Health Questionnaire), and HRQoL (MacNew Heart Disease HRQoL questionnaire) on 17 November 2021. The questionnaire was returned by 592 patients (67.1%), and 574 participants could be included in the analysis. Multivariable linear regression models were performed to investigate the associations between fatigue and depression (both exposures) and HRQoL (outcome). RESULTS: Altogether, 273 (47.6%) participants met the criteria for the presence of fatigue, about 16% showed signs of moderate to severe depression. Both fatigue and depression were significantly associated with a decreased HRQoL (total score and emotional, social, and physical subscales; all p-values < 0.0001). In particular, a combined occurrence of fatigue and depression was associated with a significantly reduced HRQoL. CONCLUSIONS: It seems necessary to screen post-MI patients for the presence of fatigue and depression in clinical practice on a routine basis to provide them with adequate support and treatment and thus also to improve their HRQoL.

[Palliative aspects in clinical acute and emergency medicine as well as intensive care medicine : Consensus paper of the DGIIN, DGK, DGP, DGHO, DGfN, DGNI, DGG, DGAI, DGINA and DGPalliativmedizin]. / Palliativmedizinische Aspekte in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin : Konsensuspapier der DGIIN, DGK, DGP, DGHO, DGfN, DGNI, DGG, DGAI, DGINA und DGPalliativmedizin.

The timely integration of palliative medicine is an important component in the treatment of various advanced diseases. While a German S­3-guideline on palliative medicine exists for patients with incurable cancer, a recommendation for non-oncological patients and especially for palliative patients presenting in the emergency department or intensive care unit is missing to date. Based on the present consensus paper, the palliative care aspects of the respective medical disciplines are addressed. The timely integration of palliative care aims to improve quality of life and symptom control in clinical acute and emergency medicine as well as intensive care.

[Palliative aspects in clinical acute and emergency medicine as well as intensive care medicine : Consensus paper of the DGIIN, DGK, DGP, DGHO, DGfN, DGNI, DGG, DGAI, DGINA and DGPalliativmedizin]. / Palliativmedizinische Aspekte in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin : Konsensuspapier der DGIIN, DGK, DGP, DGHO, DGfN, DGNI, DGG, DGAI, DGINA und DGPalliativmedizin.

The timely integration of palliative medicine is an important component in the treatment of various advanced diseases. While a German S­3-guideline on palliative medicine exists for patients with incurable cancer, a recommendation for non-oncological patients and especially for palliative patients presenting in the emergency department or intensive care unit is missing to date. Based on the present consensus paper, the palliative care aspects of the respective medical disciplines are addressed. The timely integration of palliative care aims to improve quality of life and symptom control in clinical acute and emergency medicine as well as intensive care.

[Palliative aspects in clinical acute and emergency medicine as well as intensive care medicine: consensus paper of the DGIIN, DGK, DGP, DGHO, DGfN, DGNI, DGG, DGAI, DGINA and DGPalliativmedizin]. / Palliativmedizinische Aspekte in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin: Konsensuspapier der DGIIN, DGK, DGP, DGHO, DGfN, DGNI, DGG, DGAI, DGINA und DGPalliativmedizin.

The timely integration of palliative medicine is an important component in the treatment of various advanced diseases. While a German S-3-guideline on palliative medicine exists for patients with incurable cancer, a recommendation for non-oncological patients and especially for palliative patients being treated in the emergency department or intensive care unit is missing to date. Based on the present consensus paper, the palliative care aspects of the respective medical disciplines are addressed. The timely integration of palliative care aims to improve quality of life and symptom control in clinical acute and emergency medicine as well as intensive care.

[Palliative aspects in clinical acute and emergency medicine as well as intensive care medicine : Consensus paper of the DGIIN, DGK, DGP, DGHO, DGfN, DGNI, DGG, DGAI, DGINA and DG Palliativmedizin]. / Palliativmedizinische Aspekte in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin : Konsensuspapier der DGIIN, DGK, DGP, DGHO, DGfN, DGNI, DGG, DGAI, DGINA und DG Palliativmedizin.

The integration of palliative medicine is an important component in the treatment of various advanced diseases. While a German S3 guideline on palliative medicine exists for patients with incurable cancer, a recommendation for non-oncological patients and especially for palliative patients presenting in the emergency department or intensive care unit is missing to date. Based on the present consensus paper, the palliative care aspects of the respective medical disciplines are addressed. The timely integration of palliative care aims to improve quality of life and symptom control in clinical acute and emergency medicine as well as intensive care.

Outcomes in patients with cardiac amyloidosis undergoing heart transplantation: the eurotransplant experience.

BACKGROUND: When advanced heart failure occurs in cardiac amyloidosis, prognosis is poor. In this setting heart transplantation (HTX) is a treatment option for selected patients. We here present the results of post-transplantation outcomes in cardiac amyloidosis within the Eurotransplant area, investigating possible predictors of survival. METHODS: Of 115 patients undergoing HTX due to cardiac amyloidosis in the Eurotransplant region between November 1987 and May 2020, detailed assessment prior to transplantation was available in 85 patients. The present study was conducted in a retrospective approach. Primary endpoint was mortality after HTX. Baseline variables were entered in a Cox proportional hazards model with the primary endpoint as a dependent variable. RESULTS: Median overall survival following HTX was 6.3 years in the overall collective and the subgroup. Univariate Cox proportional hazards model revealed a significant relationship between overall survival and the transplantation period (2008 to 2020 vs 1987 to 2007; median survival 9.7 years vs 1.8 years, hazard ratio 0.45, p = 0.01). Further predictors were albumin concentration (hazard ratio 0.92, p < 0.001), and systolic blood pressure (hazard ratio 0.96, p < 0.001). The transplant period as well as albumin concentration remained significant independent predictors in the AL sub cohort in a multivariate Cox proportional hazards model. CONCLUSIONS: HTX is a viable treatment option for patients at an advanced stage of cardiac amyloidosis as overall survival after transplantation has improved in the modern age. Patients at a very advanced stage of the disease, indicated by low serum albumin and blood pressure, show worse outcomes following HTX. Optimal timing and careful patient selection may therefore be particularly important to further improve post-HTX survival in amyloidosis patients.

Safety and efficacy of MitraClip in acutely ill (NYHA Class IV) patients with mitral regurgitation: Results from the global EXPAND study.

AIM: Patients with severe mitral regurgitation (MR) and acute heart failure (HF) have refractory symptoms without adequate response to medical therapy. The objective of this analysis was to assess the impact of the MitraClip device in acutely ill HF patients, characterized by NYHA Class IV at baseline, in a real-world, contemporary setting. METHODS AND RESULTS: EXPAND was a prospective, multicenter, international study enrolling patients with MR who consented to receive the MitraClip System at 57 sites globally. The study outcomes included acute procedural success (APS), quality of life, heart failure hospitalizations (HFH), and all-cause mortality. The study population comprised 1,041 patients, with 118 patients having baseline NYHA Class IV, and 922 having baseline NYHA Class I/II/III. NYHA Class IV patients had a significantly higher rate of baseline co-morbidities and secondary MR aetiology compared with NYHA Class I/II/III patients. APS was achieved in 92.4% of NYHA Class IV patients and significant improvement in MR grade to ≤Mild (1+) in 90.7% of subjects at 30 days and 92.9% at 1 year was observed. 1-year-mortality was higher in the NYHA Class IV subjects compared with the NYHA Class I/II/III subjects (29.2% vs. 17.7%, P < 0.01). Significant improvement in functional capacity assessed by NYHA Functional Class and Quality of Life assessed through KCCQ score was observed. At 1 year, 72.6% of NYHA Class IV subjects improved to NYHA Class I/II and ΔKCCQ was 31.2 (24.1, 38.3) compared with baseline. CONCLUSION: In the prospective, real-world EXPAND study, MitraClip in patients with severe MR and NYHA Class IV was found to be safe and effective in treating MR, and significantly improving QoL and long-term clinical outcomes.

Initial experience with transcatheter tricuspid valve repair in patients with cardiac amyloidosis.

AIMS: Wildtype transthyretin amyloid cardiomyopathy is an under-recognized cause of heart failure in elderly patients. Transcatheter tricuspid valve repair is a newly emerging therapeutic option for severe tricuspid regurgitation (TR). We present first insights into safety and possible benefits of this procedure in patients with cardiac amyloidosis. METHODS AND RESULTS: Eight patients with cardiac non-hereditary (wildtype) transthyretin (ATTRwt) amyloidosis and severe to torrential TR, undergoing successful transcatheter tricuspid valve repair, were included in the analysis and compared to a control group of 21 patients without cardiac amyloidosis. All patients presented with an advanced stage of amyloid cardiomyopathy. Primary endpoint was reduction in TR at 3 months follow-up. Secondary endpoints were feasibility, safety, hospitalization or death, clinical improvement, cardiac biomarkers, and structural and functional right heart parameter obtained by echocardiography. Transcatheter tricuspid valve repair resulted in a significant reduction of TR (IV to II, P = 0.008) in all eight patients with cardiac amyloidosis (100%). Device success (amyloidosis 75% vs. control group 86%, P = 0.597) and overall probability of hospitalization or death (amyloidosis 13% vs. control group 25%, P = 0.646) were similar compared with those in the control group at 3 months follow-up. Transcatheter tricuspid valve repair led to an improvement of New York Heart Association functional class (P = 0.031) and 6 min walking distance (from 313 ± 118 to 337 ± 106, P = 0.012). TR reduction in amyloidosis patients was less extensive compared with that in control group (TR-reduction 1.6 ± 0.3, P = 0.008 vs. control group 2.3 ± 0.3, P < 0.0001). Furthermore, these patients showed no significant improvement of structural right heart parameters. CONCLUSIONS: Transcatheter tricuspid valve repair is a safe and feasible new treatment option in patients with amyloid cardiomyopathy and has the potential to improve TR-grade and clinical status. However, the benefit appears to be less pronounced compared with patients without cardiac amyloidosis.

Cardiac Gene Delivery in Large Animal Models: Selective Retrograde Venous Injection.

Delivery of viral vectors to the heart represents a challenging endeavor. Besides vector design, the route of substrate administration is significantly influencing gene delivery success. The selective retrograde venous injection (SRVI) represents one of the most efficient percutaneous delivery strategies for transduction of the anterior left ventricular myocardium. In this chapter, we discuss the advantages and limitations of this vector delivery approach and provide a protocol for selective retrograde venous injection in a preclinical large animal model. As limited transgene expression frequently hampers generation of reliable proof-of-principle data and thus translation, this technique provides a valuable tool to ensure high myocardial transduction in preclinical research.

[Implantation of mechanical circulatory support systems and heart transplantation in patients with end-stage heart failure : Consensus paper of the DGK, DGTHG]. / Implantation mechanischer Unterstützungssysteme und Herztransplantation bei Patienten mit terminaler Herzinsuffizienz : Konsensuspapier DGK, DGTHG.

The treatment of patients with advanced heart failure requires interdisciplinary care in a qualified heart failure team, especially prior to and in the follow-up of mechanical circulatory support (MCS) implantation and heart transplantation (HTx). The basic prerequisite is the early specialized evaluation of symptomatic patients even under optimized heart failure treatment. Diagnostics and treatment are initially aimed at improving the prognosis. If the prerequisites for MCS or HTx treatment are present, possible contraindications and problems have to be evaluated in order to achieve an optimal risk-benefit ratio for the abovementioned complex treatments with limited resources. The optimal treatment is still HTx if the conditions are right, so this should be sought in all potential patients. At the same time, the optimal individual transplantation window should not be missed. The provision of a MCS system is a treatment performed with very good results for patients with exclusion criteria for HTx or with hemodynamic instability that prevents a longer waiting time for a donor organ. Short-term and medium-term survival is now comparable to HTx when carefully indicated. Timely implantation before the onset of manifest end-organ damage is crucial. Optimized implementation of advanced treatment requires professional structures that enable effective interdisciplinary cooperation between different sectors of health care.

Impact of Percutaneous Mitral Valve Repair Using the MitraClipTM System on Ventricular Arrhythmias and ICD Therapies.

Transcatheter edge-to-edge repair (TEER) using the MitraClip™ device has been established as a suitable alternative to mitral valve surgery in patients with severe mitral regurgitation (MR) and high or prohibitive surgical risk. Only limited information regarding the impact of TEER on ventricular arrhythmias (VA) has been reported. The aim of the present study was to assess the impact of TEER using the MitraClipTM device on the burden of VA and ICD (Implantable Cardioverter Defibrillator) therapies. Among 600 MitraClipTM implantations performed in our clinic between September 2009 and October 2018, we identified 86 patients with successful TEER and an active implantable cardiac device (pacemaker, ICD, CRT-P/D (Cardiac Resynchronization Therapy-Pacemaker/Defibrillator)) eligible for retrospective VA analyses. These patients presented with mainly functional MR (81.4%) and severely reduced left ventricular ejection fraction (mean LVEF 22.1% ± 10.3%). The observation period comprised 456 ± 313 days before and 424 ± 287 days after TEER. The burden of ventricular arrhythmias (sustained ventricular tachycardia (sVT) and ventricular fibrillation (VF)) was significantly reduced after TEER (0.85 ± 3.47 vs. 0.43 ± 2.03 events per patient per month, p = 0.01). Furthermore, the rate of ICD therapies (anti-tachycardia pacing (ATP) and ICD shock) decreased significantly after MitraClipTM implantation (1.0 ± 3.87 vs. 0.32 ± 1.41, p = 0.014). However, reduction of VA burden did not result in improved two-year survival in this patient cohort with severely reduced LVEF. Mitral valve TEER using the MitraClip™ device was associated with a significant reduction of ventricular arrhythmias and ICD therapies.

[Drop in oxygen saturation and blood pressure as well as increase in central venous pressure during mitral valve clipping in an 81-year-old female patient]. / Abfall von Sauerstoffsättigung und Blutdruck sowie Anstieg des zentralen Venendrucks im Rahmen eines Mitralklappenclippings bei einer 81-Jährigen.

BACKGROUND: Atrial septal defects (ASD) following endovascular mitral valve clipping are potentially hemodynamically relevant complications. Immediate closure with an occluder can represent a safe and effective treatment. An 81-year-old female patient suffering from severe dyspnea due to previously known severe mitral valve regurgitation was scheduled for elective mitral valve clipping. The clip was successfully implanted. Removal of the transseptal cannula resulted in a sudden drop in oxygen saturation and systolic blood pressure as well as an immediate increase in central venous pressure. An iatrogenic left-right shunt was observed at the atrial level with a relevant shunt volume. Immediate closure using an atrial septal occluder successfully restored the oxygen saturation and hemodynamic parameters. CONCLUSION: An increase in central venous pressure, reduction of systolic blood pressure or oxygen saturation after withdrawal of the transseptal cannula during mitral valve clipping should always be further investigated regarding a possible ASD.

One-year results following PASCAL-based or MitraClip-based mitral valve transcatheter edge-to-edge repair.

AIMS: Mitral valve transcatheter edge-to-edge repair (TEER) has been established as a suitable alternative to mitral valve surgery in patients with severe mitral regurgitation (MR) and high surgical risk. The PASCAL system represents a novel device, potentially augmenting the toolkit for TEER. The aim of this study was to assess and compare short and 1 year safety and efficacy of the PASCAL and MitraClip systems for TEER. METHODS AND RESULTS: Procedural, short, and 1 year outcomes of a 1:2 propensity-matched cohort including 41 PASCAL and 82 MitraClip cases were investigated. Matching was based on clinical, laboratory, echocardiographic, and functional characteristics. The primary endpoints assessed were procedural success [as defined by the Mitral Valve Academy Research Consortium (MVARC)], residual MR, functional class, and a composite endpoint comprising death, heart failure hospitalization, and mitral valve re-intervention. We found for the PASCAL and the matched MitraClip cohort no significant differences in MVARC defined technical (90.2% vs. 95.1%, P = 0.44), device (90.2% vs. 89.0%, P = 1.0), or procedural (87.8% vs. 80.5%, P = 0.45) success rates. Accordingly, the overall MR reduction and improvement in New York Heart Association (NYHA) class were comparable (1 year follow-up: MR ≤ 2 95% vs. 93.6%, P = 1.0; NYHA ≤ 2 57.1% vs. 66.7%, P = 0.59). The composite outcome revealed no statistically significant difference between both devices (1 year follow-up: 31.7% vs. 37.8%, P = 0.55). Interestingly, we found at both short and 1 year follow-up a significantly higher rate of patients with none or trace MR in the PASCAL-treated cohort (short follow-up: 17.9% vs. 0%, P = 0.0081; 1 year follow-up: 25% vs. 0%, P = 0.0016). Conversely, the rate of aborted device implantations due to an elevated transmitral gradient was higher in PASCAL interventions (9.8% vs. 1.2%, P = 0.04). CONCLUSIONS: Transcatheter edge-to-edge repair using the PASCAL or MitraClip device results in favourable and comparable outcomes regarding safety, efficacy, and clinical improvement after 1 year.