Machine learning-based prediction of in-hospital death for patients with takotsubo syndrome: The InterTAK-ML model.

AIMS: Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles. METHODS AND RESULTS: A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85-0.92), a sensitivity of 0.85 (0.78-0.95) and a specificity of 0.76 (0.74-0.79) in the internal validation cohort and an AUC of 0.82 (0.73-0.91), a sensitivity of 0.74 (0.61-0.87) and a specificity of 0.79 (0.77-0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort. CONCLUSION: A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death.

Use of CytoSorb© Hemoadsorption in Patients on Veno-Venous ECMO Support for Severe Acute Respiratory Distress Syndrome: A Systematic Review.

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality. Adjunct hemoadsorption is increasingly utilized to target underlying hyperinflammation derived from ARDS. This article aims to review available data on the use of CytoSorb© therapy in combination with V-V ECMO in severe ARDS, and to assess the effects on inflammatory, laboratory and clinical parameters, as well as on patient outcomes. A systematic literature review was conducted and reported in compliance with principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. When applicable, a before-and-after analysis for relevant biomarkers and clinical parameters was carried out. CytoSorb© use was associated with significant reductions in circulating levels of C-reactive protein and interleukin-6 (p = 0.039 and p = 0.049, respectively). Increases in PaO2/FiO2 reached significance as well (p = 0.028), while norepinephrine dosage reductions showed a non-significant trend (p = 0.067). Mortality rates in CytoSorb© patients tended to be lower than those of control groups of most included studies, which, however, were characterized by high heterogeneity and low power. In an exploratory analysis on 90-day mortality in COVID-19 patients supported with V-V ECMO, the therapy was associated with a significantly reduced risk of death. Based on the reviewed data, CytoSorb© therapy is able to reduce inflammation and potentially improves survival in ARDS patients treated with V-V ECMO. Early initiation of CytoSorb© in conjunction with ECMO might offer a new approach to enhance lung rest and promote recovery in patients with severe ARDS.

Cinefluoroscopy for assessment of mechanical heart valves with suspected dysfunction.

Background: Mechanical heart valves (MHVs) are preferred prosthesis types in many, especially younger patients who need surgical valve replacement. Although echocardiography is most frequently performed for prosthesis assessment during follow-up, ultrasound artifacts usually preclude a precise investigation of prosthesis function. Cinefluoroscopy (CF) is a simple and effective method to analyze and quantify opening and closing of prosthesis leaflets but requires careful visualization of the valve using optimal viewing angles. Here, we investigated the quality of CF studies in clinical routine and their suitability for quantitative analysis of prosthesis function. Methods and results: We retrospectively identified 94 patients with 118 cinefluoroscopies performed by 31 different investigators in one tertiary center from 2012 to 2021. Of 150 MHVs (98% bi-leaflet prostheses), 87 (58%) were aortic, 53 (34%) mitral, 7 (5%) tricuspid, and 5 (3%) pulmonary valve prostheses, respectively. CF studies were categorized by their suitability to quantitatively assess opening and closing angles. Visualization of valve function was "sufficient" in 23%, "suboptimal" in 46%, and "unsuitable" in 31% of the cases. Conclusion: In clinical routine, only one-fourth of CF studies allow for a complete assessment of leaflet motion of MHVs. Although this may be in part due to the varying experience of operators, the high number of unsuitable studies suggests that optimal viewing angles may not be achievable in all patients. Further research is required to investigate standard viewing angles and anatomy after MHV implantation to improve the quality of CF studies and reduce radiation exposure of patients and operators.

Is there a sex gap in outcomes of comparable patients supported with left ventricular assist devices?

OBJECTIVES: Historically, females were described as suffering from worse outcomes after left ventricular assist device (LVAD) implantation. However, females' preoperative conditions are unique, making direct comparisons with males challenging. This study aimed to select through propensity score (PS) matching two preoperatively comparable populations of females and males and test if any real sex-related difference exists regarding survival and adverse events after LVAD implantation. METHODS: This retrospective single-center observational study investigated patients who received LVAD implantation between 2010 and 2018. PS matching was applied to balance preoperative heterogeneity between males and females. Primary endpoint was survival at follow-up. Secondary endpoints included perioperative outcomes and LVAD-related adverse events. RESULTS: 92 fully comparable females(n = 46) and males(n = 46) were selected after PS matching (median age:57 years, min-max:18-75). 26.1% of patients required preoperative mechanical circulatory support. Females needed more intraoperative fresh frozen plasma (p < 0.001) and platelets transfusions (p = 0.008) compared to males, but postoperative outcomes were comparable between groups. In-hospital, 1 and 2-year survival were 78.3%, 69.6% and 65.2%, respectively, with no differences between groups. Survival probability remained comparable up to 8 years of follow-up (p = 0.35). Overall, females showed a higher rate of strokes (p = 0.039) compared to males in the follow-up time. CONCLUSIONS: After reducing preoperative heterogeneity between females and males, survival after LVAD implantation does not differ based on sex. However, differences might exist in terms of higher transfusions and strokes in females. Reducing preoperative sex disparities and developing intraoperative and anticoagulation strategies which acknowledge sex-related variations might help abolishing differences in LVAD outcomes.

[Uncommon tumor-associated deep vein thrombosis]. / Eine nicht alltägliche tumorassoziierte Thrombose.

Here, we report on a patient with deep vein thrombosis of the right leg, in whom diagnostic work-up revealed a previously unknown chondrosarcoma of the tibia. Physical examination revealed a firm, nondisplaceable mass on the dorsal side of the right knee that appeared as a cystic formation on ultrasound. X­ray, computed tomography, and magnetic resonance imaging were consistent with chondrosarcoma, which had likely provoked the thrombosis by local compression or paraneoplastic mechanisms. After resection of the tumor, anticoagulation was continued. In a review of all findings, a final diagnosis of highly differentiated chondrosarcoma with thrombosis of the popliteal vein was made.

Computed-Tomography as First-line Diagnostic Procedure in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Mortality after out-of-hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC) remains high despite numerous efforts to improve outcome. For patients with suspected coronary cause of arrest, coronary angiography is crucial. However, there are other causes and potentially life-threatening injuries related to cardiopulmonary resuscitation (CPR), which can be detected by routine computed tomography (CT). MATERIALS AND METHODS: At Hannover Medical School, rapid coronary angiography and CT are performed in successfully resuscitated OHCA patients as a standard of care prior to admission to intensive care. We analyzed all patients who received CT following OHCA with ROSC over a three-year period. RESULTS: There were 225 consecutive patients with return of spontaneous circulation following out-of-hospital cardiac arrest. Mean age was 64 ± 13 years, 75% were male. Of them, 174 (77%) had witnessed arrest, 145 (64%) received bystander CPR, and 123 (55%) had a primary shockable rhythm. Mean time to ROSC was 24 ± 20 min. There were no significant differences in CT pathologies in patients with or without ST-segment elevations in the initial ECG. Critical CT findings qualifying as a potential cause for cardiac arrest were intracranial bleeding (N = 6), aortic dissection (N = 5), pulmonary embolism (N = 17), pericardial tamponade (N = 3), and tension pneumothorax (N = 11). Other pathologies were regarded as consequences of CPR and relevant for further treatment: aspiration (N = 62), rib fractures (N = 161), sternal fractures (N = 50), spinal fractures (N = 11), hepatic bleeding (N = 12), and intra-abdominal air (N = 3). CONCLUSION: Early CT fallowing OHCA uncovers a high number of causes and consequences of OHCA and CPR. Those are relevant for post-arrest care and are frequently life-threatening, suggesting that CT can contribute to improving prognosis following OHCA.

Comparative Analysis of Patient Characteristics in Cardiogenic Shock Studies: Differences Between Trials and Registries.

OBJECTIVES: This study sought to evaluate the differences in cardiogenic shock patient characteristics in trial patients and real-life patients. BACKGROUND: Cardiogenic shock (CS) is a leading cause of mortality in patients presenting with acute myocardial infarction (AMI). However, the enrollment of patients into clinical trials is challenging and may not be representative of real-world patients. METHODS: We performed a systematic review of studies in patients presenting with AMI-related CS and compared patient characteristics of those enrolled into randomized controlled trials (RCTs) with those in registries. RESULTS: We included 14 RCTs (n = 2,154) and 12 registries (n = 133,617). RCTs included more men (73% vs 67.7%, P < 0.001) compared with registries. Patients enrolled in RCTs had fewer comorbidities, including less hypertension (61.6% vs 65.9%, P < 0.001), dyslipidemia (36.4% vs 53.6%, P < 0.001), a history of stroke or transient ischemic attack (7.1% vs 10.7%, P < 0.001), and prior coronary artery bypass graft surgery (5.4% vs 7.5%, P < 0.001). Patients enrolled in RCTs also had lower lactate levels (4.7 ± 2.3 mmol/L vs 5.9 ± 1.9 mmol/L, P < 0.001) and higher mean arterial pressure (73.0 ± 8.8 mm Hg vs 62.5 ± 12.2 mm Hg, P < 0.001). Percutaneous coronary intervention (97.5% vs 58.4%, P < 0.001) and extracorporeal membrane oxygenation (11.6% vs 3.4%, P < 0.001) were used more often in RCTs. The in-hospital mortality (23.9% vs 38.4%, P < 0.001) and 30-day mortality (39.9% vs 45.9%, P < 0.001) were lower in RCT patients. CONCLUSIONS: RCTs in AMI-related CS tend to enroll fewer women and lower-risk patients compared with registries. Patients enrolled in RCTs are more likely to receive aggressive treatment with percutaneous coronary intervention and extracorporeal membrane oxygenation and have lower in-hospital and 30-day mortality.

Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry.

BACKGROUND: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes. METHODS: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients. RESULTS: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients. CONCLUSION: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers. TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621.

First-in-man Implantation of a Cardiac Microcurrent Device for Chronic Systolic Heart Failure.

Current therapies significantly improve survival and clinical endpoints in patients suffering from chronic heart failure with reduced ejection fraction (HFrEF), but most are not sufficient to reverse adverse remodeling and improve myocardial contractility. Herein, we report the first-in-man experience with a novel fully implantable device for cardiac electrical microcurrent (C-MIC) application. A 79-year-old man suffering from HFrEF (dilated cardiomyopathy, NYHA class III, left ventricular ejection fraction 30%) successfully underwent implantation of the C-MIC device through left anterolateral thoracotomy. At 30-day follow-up, no device-related complications were observed, demonstrating feasibility of C-MIC implantation in a patient suffering from HFrEF.

Impella Mechanical Circulatory Support for Takotsubo Syndrome With Shock: A Retrospective Multicenter Analysis.

OBJECTIVES: To analyze the characteristics and outcome of Impella mechanical circulatory support (MCS) for Takotsubo syndrome (TS) with cardiogenic shock. BACKGROUND: TS is an acute heart failure syndrome characterized by transient severe reduction of left ventricular (LV) systolic function, with cardiogenic shock occurring in around 10% of patients. Since inotropes should be avoided due to their role in TS pathogenesis and aggravation of LV outflow tract obstruction, the use of MCS as treatment is a viable treatment option, however, studies are lacking. METHODS: The catheter-based ventricular assist device (cVAD) registry and local MCS databases were screened for TS patients with cardiogenic shock (TS-CS) supported with an Impella percutaneous ventricular assist device (pVAD). Patient and treatment characteristics and in-hospital outcomes were retrospectively analyzed. RESULTS: At 10 US and European centers, 16 TS-CS patients supported with an Impella pVAD were identified between December 2013 and May 2018 (mean age, 61.8 ± 15.5 years; 87.5% women). LV ejection fraction (LVEF) at presentation was severely reduced (mean, 19.4 ± 8.3%). Prior to MCS, 13 patients (81.3%) were mechanically ventilated, 4 patients (25.0%) had been resuscitated, and mean serum lactate was 4.7 ± 3.5 mmol/L. Mean duration of Impella support was 1.9 ± 1.0 days (range, 1-4 days). Thirteen patients (81.3%) survived to discharge, and all survivors experienced cardiac recovery with significant improvement of LVEF at discharge compared to baseline (20.4 ± 8.8 vs. 52.9 ± 12.0, P < 0.001). CONCLUSIONS: This is the first series of TS-CS patients supported with an Impella pVAD. Mortality was low, and LV systolic function recovered in all survivors. Prospective studies of Impella support in this special condition are warranted.

Impact of Atrial Fibrillation on Outcome in Takotsubo Syndrome: Data From the International Takotsubo Registry.

Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS. Methods and Results Patients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher (P<0.001), and there were fewer women (P=0.046) in the AF than in the non-AF group. Left ventricular ejection fraction was significantly lower (P=0.001), and cardiogenic shock was more often observed (P<0.001) in the AF group. Both in-hospital (P<0.001) and long-term mortality (P<0.001) were higher in the AF group. Multivariable Cox regression analysis revealed that AF was independently associated with higher long-term mortality (hazard ratio, 2.31; 95% CI, 1.50-3.55; P<0.001). Among patients with AF on admission, 42% had no known history of AF before the acute TTS event, and such patients had comparable in-hospital and long-term outcomes compared with those with a history of AF. Conclusions In patients presenting with TTS, AF on admission is significantly associated with increased in-hospital and long-term mortality rates. Whether antiarrhythmics and/or cardioversion are beneficial in TTS with AF should thus be tested in a future trial. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01947621.

Opportunities, controversies, and challenges of extracorporeal hemoadsorption with CytoSorb during ECMO.

Extracorporeal membrane oxygenation (ECMO) is frequently used in many centers around the globe for various indications. However, prognosis is often poor even with all supportive therapies, and in many cases, clinical deterioration is associated with inflammation. Hemoadsorption with CytoSorb is a novel approach to limit the inflammatory response, and the device can be safely and easily installed into ECMO circuits. CytoSorb has been used more than 130.000 times to date, but because randomized controlled trials are largely lacking, there is substantial debate on its use. Here, experts from critical care medicine, cardiology, cardiac surgery, and perfusion technology discuss the pros and cons of this novel therapy and outline the future aspects for its clinical application and research.

First in man evaluation of a novel circulatory support device: Early experience with the Impella 5.5 after CE mark approval in Germany.

BACKGROUND: The Abiomed Impella 5.5 (Danvers, MA) is a newly developed axial flow transaortic cardiac support device mounted on a 9 Fr steering catheter with a 21 Fr pump cannula. Impella 5.5 is intended for longer use and was approved for 30 days in 2018. This study evaluated the first-in-man series at six high-volume mechanical circulatory support centers in Germany after CE approval. METHODS: The first 46 consecutive patients worldwide underwent implantation in six German centers between March 2018 and September 2019 for post-CE approval evaluation. The primary end-point was 30 days and 90 days all-cause mortality. RESULTS: The mean age of patients was 59.0 ± 11.5 years, and 43 (93.4%) were men. Half of the patients had acute on chronic heart failure. The main indication for Impella 5.5 implantation was ischemic cardiomyopathy and acute myocardial infarction (47.8%). The mean support time was 15.5 ± 24.2 days (range 0-164, median 10 days (IQR = 7-19)) with a total of 712 patient-days on support. The 30 days and 90 days survival rates were 73.9% (95% CI: 63.3-88.9%) and 71.7% (95% CI: 60.7-87.1%), respectively. Additionally, 16 patients (34.8%) were weaned from the device for native heart recovery, and 19 (41.3%) were bridged to a durable device. Fifteen patients (32.6%) were mobilized to a chair, and 15 (32.6%) were ambulatory. We only noted one stroke and found no other thromboembolic complications. No aortic valve damage was observed in the study cohort. Finally, seven patients (15.2 %) had pump thrombosis, and nine (19.6 %) underwent device exchange. Sixteen patients (34.8 %) suffered from bleeding requiring transfusions during the whole treatment course. In ten patients (21.7%), the inflow cannula dislocated into the aortic root. CONCLUSIONS: The first version of the Impella 5.5 presents promising early outcomes for patients with acute heart failure and expands the spectrum of available devices. The adverse event profile is favorable for short-term devices. Dislocations have been addressed by design changes. With increasing experience with this device, our study suggests that the indications for use will expand to other cardiac shock etiologies and may improve myocardial recovery and survival in patients with cardiogenic shock.